Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.

PubMed

Charidimou, Andreas; Karayiannis, Christopher; Song, Tae-Jin; Orken, Dilek Necioglu; Thijs, Vincent; Lemmens, Robin; Kim, Jinkwon; Goh, Su Mei; Phan, Thanh G; Soufan, Cathy; Chandra, Ronil V; Slater, Lee-Anne; Haji, Shamir; Mok, Vincent; Horstmann, Solveig; Leung, Kam Tat; Kawamura, Yuichiro; Sato, Nobuyuki; Hasebe, Naoyuki; Saito, Tsukasa; Wong, Lawrence K S; Soo, Yannie; Veltkamp, Roland; Flemming, Kelly D; Imaizumi, Toshio; Srikanth, Velandai; Heo, Ji Hoe

2017-12-05

To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients ( p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs ( p = 0.001). There was no association between CMBs and recurrent ischemic stroke. The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies. © 2017 American Academy of Neurology.

Management of atrial fibrillation in Greece: the MANAGE-AF study.

PubMed

Andrikopoulos, George; Pastromas, Sokratis; Mantas, Ioannis; Sakellariou, Dimitris; Kyrpizidis, Christos; Makridis, Pantelis; Goumas, Georgios; Stakos, Dimitris; Gotsis, Alexandros; Kartalis, Athanasios; Kazianis, Georgios; Babalis, Dimitrios; Toli, Konstantina; Tzeis, Stylianos; Papavasileiou, Maria; Kalogeropoulos, Petros; Vardas, Panos

2014-01-01

Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF. Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study. The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively. The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

PubMed

Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

2014-08-01

Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF. © 2014, The American College of Clinical Pharmacology.

Decreased Mortality With Beta-Blockers in Patients With Heart Failure and Coexisting Atrial Fibrillation: An AF-CHF Substudy.

PubMed

Cadrin-Tourigny, Julia; Shohoudi, Azadeh; Roy, Denis; Talajic, Mario; Tadros, Rafik; Mondésert, Blandine; Dyrda, Katia; Rivard, Léna; Andrade, Jason G; Macle, Laurent; Guerra, Peter G; Thibault, Bernard; Dubuc, Marc; Khairy, Paul

2017-02-01

The impact of beta-blockers on mortality and hospitalizations was assessed in the largest randomized trial of patients with both atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF): the Atrial Fibrillation-Congestive Heart Failure trial. Although beta-blockers are the cornerstone of therapy for HFrEF, a recent patient-level meta-analysis cast doubt on their efficacy in patients with coexisting AF. From a total of 1,376 subjects randomized in the AF-CHF trial, those without beta-blockers at baseline were propensity matched to a maximum of 2 exposed patients. All absolute standardized differences after matching were ≤10%. Primary analyses respected the intention-to-treat principle. In on-treatment sensitivity analyses, beta-blocker status was modeled as a time-dependent covariate. Baseline characteristics were comparable among the matched cohorts (mean age 70 ± 11 years, 81% male, and mean left ventricular ejection fraction 27 ± 6%). During a median follow-up of 37 months, beta-blockers were associated with significantly lower all-cause mortality (hazard ratio [HR]: 0.721, 95% confidence interval [CI]: 0.549 to 0.945; p = 0.0180) but not hospitalizations (HR: 0.886; 95% CI: 0.715 to 1.100; p = 0.2232). Similar results were obtained in sensitivity analyses that modeled beta-blockers as a time-dependent variable (HR: 0.668 for all-cause mortality; 95% CI: 0.511 to 0.874; p = 0.0032; HR: 0.814 for hospitalizations; 95% CI: 0.653 to 1.014; p = 0.0658). There were no significant interactions between beta-blockers and patterns (i.e., persistent vs. paroxysmal) or burden of AF with respect to mortality or hospitalizations. In propensity-matched analyses, beta-blockers were associated with significantly lower mortality but not hospitalizations in patients with HFrEF and AF, irrespective of the pattern or burden of AF. These results support current evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not

Finding atrial fibrillation in stroke patients: Randomized evaluation of enhanced and prolonged Holter monitoring--Find-AF(RANDOMISED) --rationale and design.

PubMed

Weber-Krüger, Mark; Gelbrich, Götz; Stahrenberg, Raoul; Liman, Jan; Kermer, Pawel; Hamann, Gerhard F; Seegers, Joachim; Gröschel, Klaus; Wachter, Rolf

2014-10-01

Detecting paroxysmal atrial fibrillation (AF) in patients with ischemic strokes presenting in sinus rhythm is challenging because episodes are often short, occur randomly, and are frequently asymptomatic. If AF is detected, recurrent thromboembolism can be prevented efficiently by oral anticoagulation. Numerous uncontrolled studies using various electrocardiogram (ECG) devices have established that prolonged ECG monitoring increases the yield of AF detection, but most established procedures are time-consuming and costly. The few randomized trials are mostly limited to cryptogenic strokes. The optimal method, duration, and patient selection remain unclear. Repeated prolonged continuous Holter ECG monitoring to detect paroxysmal AF within an unspecific stroke population may prove to be a widely applicable, effective secondary prevention strategy. Find-AFRANDOMISED is a randomized and controlled prospective multicenter trial. Four hundred patients 60 years or older with manifest (symptoms ≥24 hours or acute computed tomography/magnetic resonance imaging lesion) and acute (symptoms ≤7 days) ischemic strokes will be included at 4 certified stroke centers in Germany. Those with previously diagnosed AF/flutter, indications/contraindications for oral anticoagulation, or obvious causative blood vessel pathologies will be excluded. Patients will be randomized 1:1 to either enhanced and prolonged Holter ECG monitoring (10 days at baseline and after 3 and 6 months) or standard of care (≥24-hour continuous ECG monitoring, according to current stroke guidelines). All patients will be followed up for at least 12 months. The primary end point is newly detected AF (≥30 seconds) after 6 months, confirmed by an independent adjudication committee. We plan to complete recruitment in autumn 2014. First results can be expected by spring 2016. Copyright © 2014 Mosby, Inc. All rights reserved.

Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

PubMed Central

Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

2014-01-01

Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.

PubMed

Wong, Ka Sing Lawrence; Hu, Dai Yi; Oomman, Abraham; Tan, Ru-San; Patel, Manesh R; Singer, Daniel E; Breithardt, Günter; Mahaffey, Kenneth W; Becker, Richard C; Califf, Robert; Fox, Keith A A; Berkowitz, Scott D; Hacke, Werner; Hankey, Graeme J

2014-06-01

In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation. © 2014 American Heart Association, Inc.

An illness-specific version of the Revised Illness Perception Questionnaire in patients with atrial fibrillation (AF IPQ-R): Unpacking beliefs about treatment control, personal control and symptom triggers.

PubMed

Taylor, Elaina C; O'Neill, Mark; Hughes, Lyndsay D; Moss-Morris, Rona

2018-04-01

This study modified the Revised Illness Perception Questionnaire (IPQ-R) in patients with persistent atrial fibrillation (AF). Qualitative interviews and think-aloud techniques informed modification of the IPQ-R to be specific to AF patients. Confirmatory Factor Analysis (CFA) (n = 198) examined the validity of the modified IPQ-R (AF-IPQ-R). Exploratory factor analysis (EFA) examined the new AF-triggers scale. Construct validity examined associations between the AF-IPQ-R, quality of life (QoL) and beliefs about medicines. Test-retest and internal reliability were examined. Interviews indicated that patients viewed triggers of AF rather than initial causes of illness as more applicable. Patients believed specific behaviours such as rest could control AF. Treatment control beliefs related to pharmacological and procedural treatments. These data were used to modify the IPQ-R subscales and to develop a triggers of AF scale. CFA indicated good model fit. EFA of the triggers scale indicated three factors: emotional; health behaviours; and over-exertion triggers. Expected correlations were found between the AF-IPQ-R, QoL and treatment beliefs, evidencing good construct validity. The AF-IPQ-R showed sound psychometric properties. It provides more detailed specification than the IPQ-R of beliefs that may help to understand poor QoL in AF patients, and guidance for future interventions in this area.

Transition of patients from blinded study drug to open-label anticoagulation: the ENGAGE AF-TIMI 48 trial.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Mercuri, Michele; Curt, Valentin; Betcher, Joshua; Grip, Laura; Cange, Abby L; Crompton, Andrea E; Murphy, Sabina A; Deenadayalu, Naveen; Antman, Elliott M

2014-08-12

At the end of 2 previous trials, an excess of stroke and bleeding was observed in patients with AF randomized to a new oral anticoagulant (NOAC) who transitioned to a vitamin K antagonist (VKA). The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial compared once-daily edoxaban to warfarin for stroke prevention in patients with AF. An end-of-trial transition plan was developed to minimize the risks of stroke due to inadequate anticoagulation and bleeding from excessive anticoagulation during this critical period. All patients on the blinded study drug at the trial's conclusion were included in this analysis. In pre-specified analyses, stroke, bleeding, and death that occurred through 30 days after the end-of-trial visit were stratified by randomized treatment allocation and open-label anticoagulant selected post-trial. Of the 13,642 patients taking the blinded study drug at the end of the trial, 9,304 (68.2%) were transitioned to open-label VKA and 4,258 patients (31.2%) to an NOAC. There were 21 strokes evenly distributed across the 3 randomized treatment arms: warfarin 7 (1.90%/year), edoxaban high dose 7 (1.89%/year), edoxaban low dose 7 (1.85%/year). Major bleeding was also similar across the 3 treatment arms: warfarin 11 (2.98%/year), edoxaban high dose 10 (2.69%/year), edoxaban low dose 18 (4.76%/year). In patients transitioned to VKA, 85% of patients had at least 1 INR ≥ 2 by day 14 after the transition and 99% by day 30. The ENGAGE AF-TIMI 48 transition plan protected patients from an excess of thrombotic and bleeding events and should be helpful in clinical practice when patients are transitioned between oral anticoagulants. (Global Study to Assess the Safety and Effectiveness of Edoxaban [DU-176b] vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [EngageAFTIMI48]; NCT00781391). Copyright © 2014 American College of Cardiology

Clinical and Economic Implications of AF Related Stroke.

PubMed

Ali, Ali N; Abdelhafiz, Ahmed

2016-01-01

A major cause of morbidity and mortality among patients with atrial fibrillation (AF) relates to the increased risk of stroke. The burden of illness that AF imparts on stroke is likely to increase with our aging populations and increasingly sophisticated cardiac monitoring techniques. Understanding the clinical and economic differences between AF related ischaemic stroke and non-AF related stroke is important if we are to improve future cost effectiveness analyses of potential preventative treatments, but also to help educate clinical and policy decision makers on use or availability of treatments to prevent AF related stroke. In this article we review the existing evidence that highlights differences in the clinical characteristics and outcomes between AF and non-AF stroke, as well as differences in their economic impact and discuss ways to improve future economic analyses.

Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention: The ROCKET AF Trial.

PubMed

Sherwood, Matthew W; Cyr, Derek D; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Washam, Jeffrey B; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Singer, Daniel E; Piccini, Jonathan P; Nessel, Christopher C; Mahaffey, Kenneth W; Patel, Manesh R

2016-08-22

The authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown. The study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial. Among 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups. In patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of rivaroxaban compared with warfarin in patients with carotid artery disease and nonvalvular atrial fibrillation: Insights from the ROCKET AF trial.

PubMed

Kochar, Ajar; Hellkamp, Anne S; Lokhnygina, Yuliya; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Singer, Daniel E; Piccini, Jonathan P; Patel, Manesh R

2018-01-01

Atrial fibrillation (AF) increases risk of stroke 5-fold. Carotid artery disease (CD) also augments the risk of stroke, yet there are limited data about the interplay of these 2 diseases and clinical outcomes in patients with comorbid AF and CD. Among patients with both AF and CD, use of rivaroxaban when compared with warfarin is associated with a lower risk of stroke. This post hoc analysis from ROCKET AF aimed to determine absolute rates of stroke/systemic embolism (SE) and bleeding, and the efficacy and safety of rivaroxaban compared with warfarin in patients with AF and CD (defined as history of carotid occlusive disease or carotid revascularization [endarterectomy and/or stenting]). A total of 593 (4.2%) patients had CD at enrollment. Patients with and without CD had similar rates of stroke or SE (adjusted hazard ratio [HR]: 0.99, 95% confidence interval [CI]: 0.66-1.48, P = 0.96), and there was no difference in major or nonmajor clinically relevant bleeding (adjusted HR: 1.04, 95% CI: 0.88-1.24, P = 0.62). The efficacy of rivaroxaban compared with warfarin for the prevention of stroke/SE was not statistically significant in patients with vs those without CD (interaction P = 0.25). The safety of rivaroxaban vs warfarin for major or nonmajor clinically relevant bleeding was similar in patients with and without CD (interaction P = 0.64). Patients with CD in ROCKET AF had similar risk of stroke/SE compared with patients without CD. Additionally, there was no interaction between CD and the treatment effect of rivaroxaban or warfarin for stroke prevention or safety endpoints. © 2018 Wiley Periodicals, Inc.

Termination of persistent atrial fibrillation during pulmonary vein isolation: insight from the MAGIC-AF trial.

PubMed

Singh, Sheldon M; d'Avila, Andre; Kim, Young-Hoon; Aryana, Arash; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Barrett, Conor D; Heist, E Kevin; Parides, Michael K; Thorpe, Kevin E; Reddy, Vivek Y

2017-10-01

Controversy on the optimal ablation strategy for persistent atrial fibrillation (AF) exists with limited work evaluating a strategy of pulmonary vein isolation (PVI) alone when AF terminates during PVI. Thirty-five patients had AF termination during PVI in the Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF; ClinicalTrials.gov number: NCT01014741) study. The objective of the current study is to report the 1-year outcome after PVI alone in this unique patient group. The 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs was reported for the 35 patients in the MAGIC-AF study with persistent AF termination during or upon completion of PVI. Freedom from recurrent atrial arrhythmia was achieved in 60% of patients where AF terminated during PVI. Cavotricuspid isthmus flutter was common when AF terminated to a macro re-entrant flutter during PVI, and responsible for 92% of all flutter circuits with AF termination. Persistent AF termination during PVI may identify a subgroup of patients who experience a similar long-term clinical outcome with PVI ablation alone when compared with other more extensive persistent AF ablation strategies. Pulmonary vein isolation alone may be an appropriate tactic in this subgroup of persistent AF patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Clinical presentation, management, and outcomes in the Indian Heart Rhythm Society-Atrial Fibrillation (IHRS-AF) registry.

PubMed

Vora, A; Kapoor, A; Nair, M; Lokhandwala, Y; Narsimhan, C; Ravikishore, A G; Dwivedi, S K; Namboodiri, N; Hygriv, R; Saxena, A; Nabar, A; Garg, S; Bardoloi, N; Yadav, R; Nambiar, A; Pandurangi, U; Jhala, D; Naik, A; Nagmallesh; Rajagopal, S; Selvaraj, R; Arora, V; Thachil, A; Thomas, J; Panicker, G

A national atrial fibrillation (AF) registry was conducted under the aegis of the Indian Heart Rhythm Society (IHRS), to capture epidemiological data-type of AF, clinical presentation and comorbidities, current treatment practices, and 1-year follow-up outcomes. A total of 1537 patients were enrolled from 24 sites in India in the IHRS-AF registry from July 2011 to August 2012. Their baseline characteristics and follow-up data were recorded in case report forms and subsequently analyzed. The average age of Indian AF patients was 54.7 years. There was a marginal female preponderance - 51.5% females and 48.5% males. At baseline, 20.4% had paroxysmal AF; 33% had persistent AF; 35.1% had permanent AF and 11% had first AF episode. At one-year follow-up, 45.6% patients had permanent AF. Rheumatic valvular heart disease (RHD) was present in 47.6% of patients. Hypertension, heart failure, coronary artery disease, and diabetes were seen in 31.4%, 18.7%, 16.2%, and 16.1%, respectively. Rate control was the strategy used in 75.2% patients, digoxin and beta-blockers being the most frequently prescribed rate-control drugs. Oral anticoagulation (OAC) drugs were used in 70% of patients. The annual mortality was 6.5%, hospitalization 8%, and incidence of stroke 1%. In India, AF patients are younger and RHD is still the most frequent etiology. Almost two-third of the patients have persistent/permanent AF. At one-year follow-up, there is a significant mortality and morbidity in AF patients in India. Copyright © 2016. Published by Elsevier B.V.

Atrial Fibrillation Management Strategies in Routine Clinical Practice: Insights from the International RealiseAF Survey

PubMed Central

Chiang, Chern-En; Naditch-Brûlé, Lisa; Brette, Sandrine; Silva-Cardoso, José; Gamra, Habib; Murin, Jan; Zharinov, Oleg J.; Steg, Philippe Gabriel

2016-01-01

Background Atrial fibrillation (AF) can be managed with rhythm- or rate-control strategies. There are few data from routine clinical practice on the frequency with which each strategy is used and their correlates in terms of patients’ clinical characteristics, AF control, and symptom burden. Methods RealiseAF was an international, cross-sectional, observational survey of 11,198 patients with AF. The aim of this analysis was to describe patient profiles and symptoms according to the AF management strategy used. A multivariate logistic regression identified factors associated with AF management strategy at the end of the visit. Results Among 10,497 eligible patients, 53.7% used a rate-control strategy, compared with 34.5% who used a rhythm-control strategy. In 11.8% of patients, no clear strategy was stated. The proportion of patients with AF-related symptoms (EHRA Class > = II) was 78.1% (n = 4396/5630) for those using a rate-control strategy vs. 67.8% for those using a rhythm-control strategy (p<0.001). Multivariate logistic regression analysis revealed that age <75 years or the paroxysmal or persistent form of AF favored the choice of a rhythm-control strategy. A change in strategy was infrequent, even in patients with European Heart Rhythm Association (EHRA) Class > = II. Conclusions In the RealiseAF routine clinical practice survey, rate control was more commonly used than rhythm control, and a change in strategy was uncommon, even in symptomatic patients. In almost 12% of patients, no clear strategy was stated. Physician awareness regarding optimal management strategies for AF may be improved. PMID:26800084

Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: Data from the GISSI-AF trial

PubMed Central

2013-01-01

Background Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. Methods We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. Results Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment

Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF.

PubMed

Jones, William Schuyler; Hellkamp, Anne S; Halperin, Jonathan; Piccini, Jonathan P; Breithardt, Gunter; Singer, Daniel E; Fox, Keith A A; Hankey, Graeme J; Mahaffey, Kenneth W; Califf, Robert M; Patel, Manesh R

2014-01-01

Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037). Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to

Contemporary stroke prevention strategies in 11 096 European patients with atrial fibrillation: a report from the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) Long-Term General Registry.

PubMed

Boriani, Giuseppe; Proietti, Marco; Laroche, Cécile; Fauchier, Laurent; Marin, Francisco; Nabauer, Michael; Potpara, Tatjana; Dan, Gheorghe-Andrei; Kalarus, Zbigniew; Diemberger, Igor; Tavazzi, Luigi; Maggioni, Aldo P; Lip, Gregory Y H

2018-05-01

Contemporary data regarding atrial fibrillation (AF) management and current use of oral anticoagulants (OACs) for stroke prevention are needed. The EURObservational Research Programme on AF (EORP-AF) Long-Term General Registry analysed consecutive AF patients presenting to cardiologists in 250 centres from 27 European countries. From 2013 to 2016, 11 096 patients were enrolled (40.7% female; mean age 69 ± 11 years). At discharge, OACs were used in 9379 patients (84.9%), with non-vitamin K antagonists (NOACs) accounting for 40.9% of OACs. Antiplatelet therapy alone was used by 20% of patients, while no antithrombotic treatment was prescribed in 6.4%. On multivariable analysis, age, hypertension, previous ischaemic stroke, symptomatic AF and planned cardioversion or ablation were independent predictors of OAC use, whereas lone AF, previous haemorrhagic events, chronic kidney disease and admission for acute coronary syndrome (ACS) or non-cardiovascular causes independently predicted OAC non-use. Regarding the OAC type, coronary artery disease, history of heart failure, or valvular heart disease, planned cardioversion and non-AF reasons for admission independently predicted the use of vitamin K antagonists (VKAs). Wide variability among the European regions was observed in the use of NOACs, independently from other clinical factors. The EORP-AF Long-Term General Registry provides a full picture of contemporary use of OAC in European AF patients. The overall rate of OACs use was generally high (84.9%), and a series of factors were associated with the prescription of OAC. A significant geographical heterogeneity in prescription of NOACs vs. VKAs was evident.

Impact of polyvascular disease on patients with atrial fibrillation: Insights from ROCKET AF.

PubMed

Chen, Sean T; Hellkamp, Anne S; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Piccini, Jonathan P; Singer, Daniel E; Patel, Manesh R

2018-06-01

We investigated the impact of polyvascular disease in patients enrolled in ROCKET AF. Cox regression models were used to assess clinical outcomes and treatment effects of rivaroxaban compared with warfarin in patients with atrial fibrillation and coronary, peripheral, or carotid artery disease, or any combination of the 3. A total of 655 (4.6%) patients had polyvascular disease (≥2 disease locations), and 3,391 (23.8%) had single-arterial bed disease. Patients with polyvascular disease had similar rates of stroke/systemic embolism but higher rates of cardiovascular and bleeding events when compared with those without vascular disease. Use of rivaroxaban compared with warfarin was associated with higher rates of stroke in patients with polyvascular disease (hazard ratio [HR] 2.41, 95% CI 1.05-5.54); however, this was not seen in patients with single-bed (HR 0.90, 95% CI 0.64-1.28) or no vascular disease (HR 0.85, 95% CI 0.69-1.04; interaction P = .058). There was a significant interaction for major or nonmajor clinically relevant bleeding in patients with polyvascular (HR 1.23, 95% CI 0.91-1.65) and single-bed vascular disease (HR 1.30, 95% CI 1.13-1.49) treated with rivaroxaban compared with warfarin when compared with those without vascular disease (HR 0.95, 95% CI 0.87-1.04; interaction P = .0006). Additional antiplatelet therapy in this population did not improve stroke or cardiovascular outcomes. The use of rivaroxaban compared with warfarin was associated with a higher risk of stroke and bleeding in patients with polyvascular disease enrolled in ROCKET AF. Further studies are needed to understand the optimal management of this high-risk population. Copyright © 2018 Elsevier Inc. All rights reserved.

Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

PubMed

Spencer, Ryan J; Amerena, John V

2015-12-01

Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

Polish and European management strategies in patients with atrial fibrillation. Data from the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot).

PubMed

Lenarczyk, Radosław; Mitręga, Katarzyna; Mazurek, Michał; Janion, Marianna; Opolski, Grzegorz; Drożdż, Jarosław; Streb, Witold; Fuglewicz, Artur; Sokal, Adam; Laroche, Cécile; Lip, Gregory Y H; Kalarus, Zbigniew

2016-01-01

Despite continued efforts of the European Society of Cardiology (ESC) to unify management of patients with atrial fibrillation (AF) across Europe, interregional differences in guideline adherence are likely. The aim of the study was to compare treatment strategies depending on baseline characteristics of AF patients between Poland and other members of the European Union (EU). We analyzed the baseline data and treatment strategies in participants of the ESC registry: the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. A total of 3119 consecutive patients with AF diagnosed within the last year were included in 67 centers from 9 countries, including 419 patients enrolled in 15 Polish centers. A rhythm control strategy was more frequent in Poland than in other EU countries (20.8% vs 11.9%; P <0.0001). Catheter ablation for AF was also used more frequently in Polish cardiology wards (13.9% vs 8.3%; P = 0.0017), while amiodarone at discharge was used less frequently (12.0% vs 22.7%; P <0.0001). In-hospital use of vitamin K antagonists (VKAs) and non-VKA anticoagulants was less frequent in Polish patients with a CHA2DS2-VASc score of 2 or higher than in patients from other EU countries (61.1% vs 79.0%; P <0.0001), but overall anticoagulation rates at discharge were similar to those in other countries (83.3% vs 82.6%). A rhythm control-oriented strategy in patients with AF with the use of ablation in cardiology wards is more frequent in Poland than in other EU countries. Similar to other EU countries, compliance with the ESC guidelines regarding anticoagulation in AF patients is suboptimal in Poland. Undertreatment was observed in a significant proportion of patients at high risk of stroke, while a large group of low-risk patients are overtreated. Differences between the types of recruiting centers in Poland and other EU countries might have influenced the results.

Hyperuricemia and the risk of ischemic stroke in patients with atrial fibrillation--could it refine clinical risk stratification in AF?

PubMed

Chao, Tze-Fan; Liu, Chia-Jen; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Chen, Tzeng-Ji; Tsao, Hsuan-Ming; Chen, Shih-Ann

2014-01-01

Although hyperuricemia has been reported to be a risk factor of stroke, the relationship between hyperuricemia and stroke in patients with atrial fibrillation (AF) remains uncertain. The goal of the present study was to investigate whether hyperuricemia could potentially refine clinical risk stratification in AF. This study used the "National Health Insurance Research Database" in Taiwan. A total of 7601 AF patients who did not receive antiplatelet agents or oral anticoagulants were identified as the study population. Hyperuricemia was defined as having at least one episode of gout attack necessitating long-term treatment with uric acid-lowering agents. The association between hyperuricemia and ischemic stroke was analyzed. During the follow up of 3.0±2.7 years, 1116 patients (14.7%) experienced ischemic stroke with an annual rate of around 4.9%. Hyperuricemia significantly predicts stroke, with a hazard ratio (HR) of 1.280 after adjusting for CHA2DS2-VASc score and other comorbidities. Among the 376 patients with a CHA2DS2VASc score of 0, hyperuricemia can further stratify them into 2 groups with different stroke rates (7.1% versus 1.3%, p=0.020). The adjusted HR of hyperuricemia in predicting ischemic stroke diminished from 7.491 for patients with a CHA2DS2-VASc score of 0 to 1.659 for those with a score of 3, and became insignificant for patients with a score ≥4. Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF. It deserves a prospective trial to investigate whether it would change the current strategy for stroke preventions using oral anticoagulants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48

PubMed Central

Gupta, Deepak K.; Shah, Amil M.; Giugliano, Robert P.; Ruff, Christian T.; Antman, Elliott M.; Grip, Laura T.; Deenadayalu, Naveen; Hoffman, Elaine; Patel, Indravadan; Shi, Minggao; Mercuri, Michele; Mitrovic, Veselin; Braunwald, Eugene; Solomon, Scott D.

2014-01-01

Aims The complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF. Methods and results Left atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF (R = −0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography. Conclusions In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients. Clinical Trial Registration: http://www.clinicaltrials.gov; ID = NCT00781391. PMID:24302269

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

PubMed

Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R; Becker, Richard C; Breithardt, Günter; Carolei, Antonio; Diener, Hans-Christoph; Donnan, Geoffrey A; Halperin, Jonathan L; Mahaffey, Kenneth W; Mas, Jean-Louis; Massaro, Ayrton; Norrving, Bo; Nessel, Christopher C; Paolini, John F; Roine, Risto O; Singer, Daniel E; Wong, Lawrence; Califf, Robert M; Fox, Keith A A; Hacke, Werner

2012-04-01

In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08

Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

PubMed

Fitzmaurice, David A; Accetta, Gabriele; Haas, Sylvia; Kayani, Gloria; Lucas Luciardi, Hector; Misselwitz, Frank; Pieper, Karen; Ten Cate, Hugo; Turpie, Alexander G G; Kakkar, Ajay K

2016-08-01

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably. © 2016 John Wiley & Sons Ltd.

Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

PubMed

Uchiyama, Shinichiro; Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

2014-01-01

The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Low Body Weight Is Associated With the Incidence of Stroke in Atrial Fibrillation Patients - Insight From the Fushimi AF Registry.

PubMed

Hamatani, Yasuhiro; Ogawa, Hisashi; Uozumi, Ryuji; Iguchi, Moritake; Yamashita, Yugo; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru; Morita, Satoshi; Akao, Masaharu

2015-01-01

Japanese patients with atrial fibrillation (AF) are generally small and lean, but knowledge of the clinical characteristics of those with low body weight (LBW: ≤50 kg) is limited. The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions in Fushmi-ku, Japan. The BW and follow-up data were available for 2,945 patients. We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group. Patients in the LBW group accounted for 26.8% (788 patients) of the total. The LBW group was more often female, older, and had higher CHADS2score. The incidence of stroke/systemic embolism (SE) during follow-up was higher in the LBW group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.57-3.04; P<0.01), whereas that of major bleeding was comparable (HR: 1.05, 95% CI: 0.64-1.68; P=0.84). This trend was consistently observed in the subgroups stratified by age, sex, and oral anticoagulant prescription at baseline. Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE. Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE, but the incidence of major bleeding was not particularly high.

Correlation between IL-17A/F, IL-23, IL-35 and IL-12/-23 (p40) levels in peripheral blood lymphocyte cultures and disease activity in Behcet's patients.

PubMed

Sonmez, Cemile; Yucel, Aysegul Atak; Yesil, Turan Hilmi; Kucuk, Hamit; Sezgin, Berna; Mercan, Ridvan; Yucel, Ahmet Eftal; Demirel, Gulderen Yanikkaya

2018-03-20

Behcet's disease is a chronic multisystemic disease with remissions and relapses. Several studies have shown that immune mechanisms play an important role in the development of the disease. In order to assess the association of disease activity with IL-17A/F, IL-23, IL-12/23 (p40) and IL-35 expression, we aimed to investigate production of these cytokines in peripheral blood mononuclear cells (PBMCs) from Behcet's patients and normal controls. Furthermore, we included Systemic Lupus Erythematosus (SLE) as disease control to evaluate the specificity of our data for immunopathogenesis of BD. Totally 15 active, 15 inactive Behcet's patients, 12 active and 12 inactive SLE patients and 12 healthy volunteers were enrolled in the study. Peripheral blood mononuclear cells were separated, lymphocyte cultures were performed and IL-17A/F, IL-12/23 p(40), IL-23, IL-35 cytokine levels were measured by ELISA in culture supernatants in the presence or absence of phytohemagglutinin (PHA) on time-dependent manner. IL-17 A/F levels increased parallel to IL-23 levels in Behcet's and SLE patients. Compared to healthy controls, IL-17 A/F levels were higher in active Behcet's and SLE patients; on the contrary, levels of IL-35 were lower. IL-17A/F, IL-12/23 (p40) and IL-23 levels were detectable most frequently in active Behcet's patients followed by active SLE patients. Our results indicate that IL-17 A/F, IL-23 and IL-12/23 (p40) may play role in the immunopathogenesis of BD so as Th17 and Th1 cell responses. Since IL-35 levels were lower in active Behcet's patients compared to inactive patients and healthy controls, there may be a plasticity between Th17 and Treg cells according to the state of disease activity.

Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE-AF) randomized trial: Design and rationale.

PubMed

Bernstein, Richard A; Kamel, Hooman; Granger, Christopher B; Kowal, Robert C; Ziegler, Paul D; Schwamm, Lee H

2017-08-01

Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial. STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for ≥12 months and up to 3 years. The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms. This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

PubMed

Piccini, Jonathan P; Connolly, Stuart J; Abraham, William T; Healey, Jeff S; Steinberg, Benjamin A; Al-Khalidi, Hussein R; Dignacco, Patricia; van Veldhuisen, Dirk J; Sauer, William H; White, Michel; Wilton, Stephen B; Anand, Inder S; Dufton, Christopher; Marshall, Debra A; Aleong, Ryan G; Davis, Gordon W; Clark, Richard L; Emery, Laura L; Bristow, Michael R

2018-05-01

Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501). Copyright © 2017 Elsevier Inc. All rights reserved.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Hughey, Andrew B; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Ahsan, Syed; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2018-06-14

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI 2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI 2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI 2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

PubMed

Narasimhan, C; Verma, Jagmohan Singh; Ravi Kishore, A G; Singh, Balbir; Dani, Sameer; Chawala, Kamaldeep; Haque, Azizul; Khan, Aftab; Nair, Mohan; Vora, Amit; Rajasekhar, V; Thomas, Joy M; Gupta, Anoop; Naik, Ajay; Prakash, V S; Naditch, Lisa; Gabriel Steg, P

Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS 2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke. Copyright © 2016. Published by Elsevier B.V.

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

PubMed

Ten Cate, V; Ten Cate, H; Verheugt, F W A

2016-10-01

There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

Clinical events after interruption of anticoagulation in patients with atrial fibrillation: An analysis from the ENGAGE AF-TIMI 48 trial.

PubMed

Cavallari, Ilaria; Ruff, Christian T; Nordio, Francesco; Deenadayalu, Naveen; Shi, Minggao; Lanz, Hans; Rutman, Howard; Mercuri, Michele F; Antman, Elliott M; Braunwald, Eugene; Giugliano, Robert P

2018-04-15

Patients with atrial fibrillation (AF) who interrupt anticoagulation are at high risk of thromboembolism and death. Patients enrolled in the ENGAGE AF-TIMI 48 trial (randomized comparison of edoxaban vs. warfarin) who interrupted study anticoagulant for >3 days were identified. Clinical events (ischemic stroke/systemic embolism, major cardiac and cerebrovascular events [MACCE]) were analyzed from day 4 after interruption until day 34 or study drug resumption. During 2.8 years median follow-up, 13,311 (63%) patients interrupted study drug for >3 days. After excluding those who received open-label anticoagulation during the at-risk window, the population for analysis included 9148 patients. The rates of ischemic stroke/systemic embolism and MACCE post interruption were substantially greater than in patients who never interrupted (15.42 vs. 0.26 and 60.82 vs. 0.36 per 100 patient-years, respectively, p adj  < .001). Patients who interrupted study drug for an adverse event (44.1% of the cohort), compared to those who interrupted for other reasons, had an increased risk of MACCE (HR adj 2.75; 95% CI 2.02-3.74, p < .0001), but similar rates of ischemic stroke/systemic embolism. Rates of clinical events after interruption of warfarin and edoxaban were similar. Interruption of study drug was frequent in patients with AF and was associated with a substantial risk of major cardiac and cerebrovascular events over the ensuing 30 days. This risk was particularly high in patients who interrupted as a result of an adverse event; these patients deserve close monitoring and resumption of anticoagulation as soon as it is safe to do so. Copyright © 2018 Elsevier B.V. All rights reserved.

Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

PubMed

Kim, M H; Lin, J; Hussein, M; Battleman, D

2009-12-01

Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). As a retrospective analysis, the study is subject to potential selection bias, while its reliance on

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

PubMed

Swerdlow, C D; Schsls, W; Dijkman, B; Jung, W; Sheth, N V; Olson, W H; Gunderson, B D

2000-02-29

To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT).

PubMed

Guhl, Emily N; Schlusser, Courtney L; Henault, Lori E; Bickmore, Timothy W; Kimani, Everlyne; Paasche-Orlow, Michael K; Magnani, Jared W

2017-11-01

Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the Embodied Conversational Agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT)

PubMed Central

Guhl, Emily N.; Schlusser, Courtney L.; Henault, Lori E.; Bickmore, Timothy W.; Kimani, Everlyne; Paasche-Orlow, Michael K.; Magnani, Jared W.

2017-01-01

Background Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. Design The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the embodied conversational agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. Conclusions The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. PMID:28923492

Heart rate-reducing effects of bisoprolol in Japanese patients with chronic atrial fibrillation: results of the MAIN-AF study.

PubMed

Yamashita, Takeshi; Inoue, Hiroshi

2013-07-01

A variety of β-blockers are used to control heart rate (HR) in atrial fibrillation (AF); however, there have been few quantitative assessments of HR and blood pressure reductions with β-blocker monotherapy. Seventy-eight patients with chronic (persistent or permanent) AF were administered bisoprolol (2.5mg/day) for 2 weeks. Subsequently, 48 patients judged to require a dose increase were either continued on 2.5mg/day (24 patients) or administered a higher dose (5mg/day; 24 patients) in a double-blind fashion for two further weeks. Change in mean HR as determined by Holter electrocardiogram was the primary endpoint. After 2 weeks of bisoprolol 2.5mg/day, mean HR was significantly lower than that before treatment (12.2±9.1beats/min, p<0.001). Mean HRs in the 5-mg and 2.5-mg continuation groups were also significantly decreased compared with those before treatment (17.3±12.9 and 11.4±7.4beats/min, respectively, both p<0.001), with a significant between-group difference (p=0.033). The HR reduction was greater during the day than at night. Although a greater reduction in systolic blood pressure was seen in the 5-mg group than in the 2.5-mg continuation group, the difference between groups was not significant. There were no serious adverse events. This is the first quantitative analysis of β-blocker monotherapy in AF patients. Bisoprolol exhibits a dose-responsive HR reduction when administered at sequential doses of 2.5mg/day and 5mg/day. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial.

PubMed

Sherwood, Matthew W; Nessel, Christopher C; Hellkamp, Anne S; Mahaffey, Kenneth W; Piccini, Jonathan P; Suh, Eun-Young; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hankey, Graeme J; Berkowitz, Scott D; Fox, Keith A A; Patel, Manesh R

2015-12-01

Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation. Copyright © 2015 American College of Cardiology Foundation. Published by

An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

PubMed

Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

2017-07-01

Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C <1%) and a history of at least 150 exposure-days to any FVIII-containing product. Eligible patients received a single dose of moroctocog alfa (AF-CC) 50 IU/kg IV within 10 minutes. Blood samples were collected within 2 hours before administration and through 72 hours after dosing. Pharmacokinetic parameters were assessed based on FVIII:C and were analyzed by age groups: ages 6 to <12 years (n = 3) and ≥12 years (n = 10). The mean plasma concentration-time profile for FVIII:C activity was consistently lower in patients aged 6 to <12 years compared with those aged ≥12 years. Geometric AUC 0-∞ and C max were approximately 57% and 28% lower in the younger patients relative to the older patients, respectively. A total of 4 adverse events occurred in 4 patients. Low-titer, transient FVIII inhibitors were observed in 2 patients and were considered serious adverse events. Neither case resulted in clinical manifestations nor required treatment. This is the first report of the pharmacokinetic parameters of FVIII:C after moroctocog alfa (AF-CC) in an all-Chinese population of males with hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported

Predictors of arrhythmia recurrence after balloon cryoablation of atrial fibrillation: the value of CAAP-AF risk scoring system.

PubMed

Sanhoury, Mohamed; Moltrasio, Massimo; Tundo, Fabrizio; Riva, Stefania; Dello Russo, Antonio; Casella, Michela; Tondo, Claudio; Fassini, Gaetano

2017-08-01

In the present study, we aimed to test the value of CAAP-AF score for prediction of atrial fibrillation (AF) recurrence at follow-up in a group of our patients treated by balloon cryoablation. A total of 283 symptomatic drug-refractory AF patients [261 (92%) with paroxysmal AF] who underwent pulmonary vein isolation (PVI) with second-generation cryoballoon between April 2012 and October 2016 were included. The CAAP-AF score was calculated for every patient. A total of 283 patients [68 female (20%), mean age 59.8 ± 11.4 years] were included in the present analysis. Eighty-nine patients (31%) had hypertension and 13 (4%) had coronary artery disease. The mean left atrial diameter and left ventricular ejection fraction were 40.6 ± 7.0 mm and 60.0 ± 9.1%, respectively. The mean CHA 2 DS 2 -VASc score was 1.2 ± 1.1, and mean number of prior failed antiarrhythmic drugs was 1.4 ± 0.8. At 18 ± 6 months follow-up, 25 patients (8.87%) developed AF recurrence. The recurrence rate was as follows: 3.17% (score 0-3), 8.47% (score 4), 16.28% (score 5), 6.67% (score 6), 23.08% (score 7), and 36.36% (score ≥8). The recurrence rate was 4.86% at a score <5 and 16.49% at a value ≥5; a score cutoff ≥5 predicted AF recurrence with a sensitivity 64% and specificity 68%. The present analysis suggests the usefulness of CAAP-AF scoring system, with its simple and easily obtained six clinical variables, to predict AF recurrence after PVI by means of second-generation cryoballoon. A score value ≥5 predicted AF recurrence with a sensitivity 64% and specificity 68%.

Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

PubMed

Potpara, Tatjana S; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S; Polovina, Marija M; Petranov, Stanislav L; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y H

2016-02-12

Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

Health Information in Somali (Af-Soomaali )

MedlinePlus

... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Pendulum Exercises for Shoulder - Af-Soomaali (Somali) Bilingual PDF ... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Pendulum Exercises for Shoulder - Af-Soomaali (Somali) Bilingual PDF ...

Treatment Failure With Rhythm and Rate Control Strategies in Patients With Atrial Fibrillation and Congestive Heart Failure: An AF-CHF Substudy.

PubMed

Dyrda, Katia; Roy, Denis; Leduc, Hugues; Talajic, Mario; Stevenson, Lynne Warner; Guerra, Peter G; Andrade, Jason; Dubuc, Marc; Macle, Laurent; Thibault, Bernard; Rivard, Lena; Khairy, Paul

2015-12-01

Rate and rhythm control strategies for atrial fibrillation (AF) are not always effective or well tolerated in patients with congestive heart failure (CHF). We assessed reasons for treatment failure, associated characteristics, and effects on survival. A total of 1,376 patients enrolled in the AF-CHF trial were followed for 37  ±  19 months, 206 (15.0%) of whom failed initial therapy leading to crossover. Rhythm control was abandoned more frequently than rate control (21.0% vs. 9.1%, P < 0.0001). Crossovers from rhythm to rate control were driven by inefficacy, whereas worsening heart failure was the most common reason to crossover from rate to rhythm control. In multivariate analyses, failure of rhythm control was associated with female sex, higher serum creatinine, functional class III or IV symptoms, lack of digoxin, and oral anticoagulation. Factors independently associated with failure of rate control were paroxysmal (vs. persistent) AF, statin therapy, and presence of an implantable cardioverter-defibrillator. Crossovers were not associated with cardiovascular mortality (hazard ratio [HR] 1.11 from rhythm to rate control; 95% confidence interval [95% CI, 0.73-1.73]; P = 0.6069; HR 1.29 from rate to rhythm control; 95% CI, 0.73-2.25; P = 0.3793) or all-cause mortality (HR 1.16 from rhythm to rate control, 95% CI [0.79-1.72], P = 0.4444; HR 1.15 from rate to rhythm control, 95% [0.69, 1.91], P = 0.5873). Rhythm control is abandoned more frequently than rate control in patients with AF and CHF. The most common reasons for treatment failure are inefficacy for rhythm control and worsening heart failure for rate control. Changing strategies does not impact survival. © 2015 Wiley Periodicals, Inc.

The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey.

PubMed

Potpara, Tatjana S; Trendafilova, Elina; Dan, Gheorghe-Andrei; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Gjini, Viktor; Pojskic, Belma; Popescu, Mircea Ioakim; Georgescu, Catalina Arsenescu; Dimitrova, Elena S; Kamenova, Delyana; Ekmeciu, Uliks; Mrsic, Denis; Nenezic, Ana; Brusich, Sandro; Milanov, Srdjan; Zeljkovic, Ivan; Lip, Gregory Y H

2017-08-01

Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial

PubMed Central

Mahaffey, Kenneth W.; Stevens, Susanna R.; White, Harvey D.; Nessel, Christopher C.; Goodman, Shaun G.; Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Califf, Robert M.; Fox, Keith A.A.; Breithardt, Günter

2014-01-01

Aims We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. Methods and results In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73–1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59–3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Conclusion Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events. PMID:24132190

Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial.

PubMed

Mahaffey, Kenneth W; Stevens, Susanna R; White, Harvey D; Nessel, Christopher C; Goodman, Shaun G; Piccini, Jonathan P; Patel, Manesh R; Becker, Richard C; Halperin, Jonathan L; Hacke, Werner; Singer, Daniel E; Hankey, Graeme J; Califf, Robert M; Fox, Keith A A; Breithardt, Günter

2014-01-01

We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events.

Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation for the secondary prevention of stroke: a subgroup analysis of J-ROCKET AF.

PubMed

Tanahashi, Norio; Hori, Masatsugu; Matsumoto, Masayasu; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

2013-11-01

The overall analysis of the rivaroxaban versus warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial revealed that rivaroxaban was not inferior to warfarin with respect to the primary safety outcome. In addition, there was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban compared with warfarin. In this subanalysis of the J-ROCKET AF trial, we investigated the consistency of safety and efficacy profile of rivaroxaban versus warfarin among the subgroups of patients with previous stroke, transient ischemic attack, or non-central nervous system systemic embolism (secondary prevention group) and those without (primary prevention group). Patients in the secondary prevention group were 63.6% of the overall population of J-ROCKET AF. In the secondary prevention group, the rate of the principal safety outcome (% per year) was 17.02 in rivaroxaban-treated patients and 18.26 in warfarin-treated patients (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.70-1.29), while the rate of the primary efficacy endpoint was 1.66 in rivaroxaban-treated patients and 3.25 in warfarin-treated patients (HR 0.51; 95% CI 0.23-1.14). There were no significant interactions in the principal safety and the primary efficacy endpoints of rivaroxaban compared to warfarin between the primary and secondary prevention groups (P=.090 and .776 for both interactions, respectively). The safety and efficacy profile of rivaroxaban compared with warfarin was consistent among patients in the primary prevention group and those in the secondary prevention group. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Peri-operative Adverse Outcomes in Patients with Atrial Fibrillation Taking Warfarin or Edoxaban: Analysis of the ENGAGE AF-TIMI 48 Trial.

PubMed

Douketis, James D; Murphy, Sabina A; Antman, Elliott M; Grip, Laura T; Mercuri, Michele F; Ruff, Christian T; Weitz, Jeffrey I; Braunwald, Eugene; Giugliano, Robert P

2018-06-01

 Peri-operative management of anticoagulated patients with atrial fibrillation (AF) is challenging. To gain information on the peri-operative management of edoxaban, we compared outcomes in patients on warfarin or edoxaban enrolled in ENGAGE AF-TIMI 48 who underwent a surgery or invasive procedure.  Data from patients undergoing their first surgery/procedure were analysed and results compared by anticoagulant (warfarin vs. higher- or lower-dose edoxaban regimen [HDER and LDER, respectively]). Patients were classified by procedural management: anticoagulant interrupted (last dose 4-10 days pre-procedure) or anticoagulant continued (last dose ≤ 3 days pre-procedure). Stroke/systemic embolism (SSE), major bleeding (MB), MB or clinically relevant non-MB (CRNMB) and death were assessed from 7 days pre- until 30 days post-procedure. The chi-square test was used to compare outcomes across treatment groups.  A total of 7,193 patients (34%) underwent surgery/procedure: 3,116 had anticoagulant interrupted, 4,077 had anticoagulant continued. Among patients on warfarin, HDER and LDER who had anticoagulant interrupted, rates of SSE were 0.6, 0.5 and 0.9% ( p  = 0.53), rates of MB were 1.0, 1.2 and 1.1% ( p  = 0.94) and rates of MB or CRNMB were 3.9, 4.2 and 3.6% ( p  = 0.78); among patients on warfarin, HDER and LDER who had anticoagulant continued, rates of SSE were 1.1, 0.7 and 0.9% ( p  = 0.51), rates of MB were 3.6, 2.6 and 2.4% ( p  = 0.13) and rates of MB or CRNMB were 8.5, 7.9 and 6.6% ( p  = 0.17).  In patients requiring surgery/procedure in ENGAGE AF-TIMI 48, peri-operative rates of SSE, MB and death were not significantly different in patients who received edoxaban or warfarin. Schattauer GmbH Stuttgart.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

PubMed Central

Deeks, Jonathan J; Griffith, Michael; Lip, Gregory YH; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-01-01

Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. Ethics and dissemination

Topological ferrimagnetic behaviours of coordination polymers containing manganese(II) chains with mixed azide and carboxylate bridges and alternating F/AF/AF'/AF'/AF interactions.

PubMed

Wang, Yan-Qin; Liu, Hou-Ting; Qi, Yan; Gao, En-Qing

2014-08-21

Two Mn(ii) complexes with azide and a new zwitterionic tetracarboxylate ligand 1,2,4,5-tetrakis(4-carboxylatopyridinium-1-methylene)benzene (L(1)), {[Mn5(L(1))2(N3)8(OH)2]·12H2O}n () and {[Mn5(L(1))2(N3)8(H2O)2](ClO4)2·6H2O}n (), have been synthesized and characterized crystallographically and magnetically. and contain similar alternating chains constructed by azide and carboxylate bridges. The independent sets of bridges alternate in an ABCCB sequence between adjacent Mn(ii) ions: (EO-N3)2 double bridges (EO = end-on) (denoted as A), [(EO-N3)(OCO)2] triple bridges (denoted as B) and [(EO-N3)(OCO)] double bridges (denoted as C). The alternating chains are interlinked into 2D coordination networks by the tetrapyridinium spacers. Magnetic studies demonstrate that the magnetic coupling through the double EO azide bridges is ferromagnetic and that through mixed azide/carboxylate bridges is antiferromagnetic. The unprecedented F/AF/AF'/AF'/AF coupling sequence along the chain dictates an uncompensated ground spin state (S = 5/2 per Mn5 unit) and leads to one-dimensional topological ferrimagnetism, which features a minimum in the χT versus T plot.

Risk factors for death, stroke, and bleeding in 28,628 patients from the GARFIELD-AF registry: Rationale for comprehensive management of atrial fibrillation.

PubMed

Bassand, Jean-Pierre; Accetta, Gabriele; Al Mahmeed, Wael; Corbalan, Ramon; Eikelboom, John; Fitzmaurice, David A; Fox, Keith A A; Gao, Haiyan; Goldhaber, Samuel Z; Goto, Shinya; Haas, Sylvia; Kayani, Gloria; Pieper, Karen; Turpie, Alexander G G; van Eickels, Martin; Verheugt, Freek W A; Kakkar, Ajay K

2018-01-01

The factors influencing three major outcomes-death, stroke/systemic embolism (SE), and major bleeding-have not been investigated in a large international cohort of unselected patients with newly diagnosed atrial fibrillation (AF). In 28,628 patients prospectively enrolled in the GARFIELD-AF registry with 2-year follow-up, we aimed at analysing: (1) the variables influencing outcomes; (2) the extent of implementation of guideline-recommended therapies in comorbidities that strongly affect outcomes. Median (IQR) age was 71.0 (63.0 to 78.0) years, 44.4% of patients were female, median (IQR) CHA2DS2-VASc score was 3.0 (2.0 to 4.0); 63.3% of patients were on anticoagulants (ACs) with or without antiplatelet (AP) therapy, 24.5% AP monotherapy, and 12.2% no antithrombotic therapy. At 2 years, rates (95% CI) of death, stroke/SE, and major bleeding were 3.84 (3.68; 4.02), 1.27 (1.18; 1.38), and 0.71 (0.64; 0.79) per 100 person-years. Age, history of stroke/SE, vascular disease (VascD), and chronic kidney disease (CKD) were associated with the risks of all three outcomes. Congestive heart failure (CHF) was associated with the risks of death and stroke/SE. Smoking, non-paroxysmal forms of AF, and history of bleeding were associated with the risk of death, female sex and heavy drinking with the risk of stroke/SE. Asian race was associated with lower risks of death and major bleeding versus other races. AC treatment was associated with 30% and 28% lower risks of death and stroke/SE, respectively, compared with no AC treatment. Rates of prescription of guideline-recommended drugs were suboptimal in patients with CHF, VascD, or CKD. Our data show that several variables are associated with the risk of one or more outcomes, in terms of death, stroke/SE, and major bleeding. Comprehensive management of AF should encompass, besides anticoagulation, improved implementation of guideline-recommended therapies for comorbidities strongly associated with outcomes, namely CHF, VascD, and CKD

The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2.

PubMed

Huisman, Menno V; Rothman, Kenneth J; Paquette, Miney; Teutsch, Christine; Diener, Hans-Christoph; Dubner, Sergio J; Halperin, Jonathan L; Ma, Chang Sheng; Zint, Kristina; Elsaesser, Amelie; Bartels, Dorothee B; Lip, Gregory Y H

2017-02-21

GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available. This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients' baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA 2 DS 2 -VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score ≥2; 86.1%); 13.9% had moderate risk (CHA 2 DS 2 -VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and

Evolution of AF6-RAS association and its implications in mixed-lineage leukemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Matthew J.; Ottoni, Elizabeth; Ishiyama, Noboru

Elucidation of activation mechanisms governing protein fusions is essential for therapeutic development. MLL undergoes rearrangement with numerous partners, including a recurrent translocation fusing the epigenetic regulator to a cytoplasmic RAS effector, AF6/afadin. We show here that AF6 employs a non-canonical, evolutionarily conserved α-helix to bind RAS, unique to AF6 and the classical RASSF effectors. Further, all patients with MLL-AF6 translocations express fusion proteins missing only this helix from AF6, resulting in exposure of hydrophobic residues that induce dimerization. We provide evidence that oligomerization is the dominant mechanism driving oncogenesis from rare MLL translocation partners and employ our mechanistic understanding ofmore » MLL-AF6 to examine how dimers induce leukemia. Proteomic data resolve association of dimerized MLL with gene expression modulators, and inhibiting dimerization disrupts formation of these complexes while completely abrogating leukemogenesis in mice. Oncogenic gene translocations are thus selected under pressure from protein structure/function, underscoring the complex nature of chromosomal rearrangements.« less

Complex Transcriptional Control of the Antibiotic Regulator afsS in Streptomyces: PhoP and AfsR Are Overlapping, Competitive Activators▿

PubMed Central

Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F.

2011-01-01

The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the −35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named “superAfsR”). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity (“superPhoP”). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites. PMID:21378195

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

PubMed

Main, Michael L; Fan, Dali; Reddy, Vivek Y; Holmes, David R; Gordon, Nicole T; Coggins, Tina R; House, John A; Liao, Lawrence; Rabineau, Dawn; Latus, George G; Huber, Kenneth C; Sievert, Horst; Wright, Richard F; Doshi, Shephal K; Douglas, Pamela S

2016-04-01

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF

Effects of Iron Depletion on CALM-AF10 Leukemias

PubMed Central

Heath, Jessica L.; Weiss, Joshua M.

2014-01-01

Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis (CME). The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by CME. CALM-AF10 leukemias harbor a single copy of the normal CALM gene, and may therefore be more sensitive to the growth inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that Calm heterozygous (CalmHET) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor (sTfR) levels and reduced growth rates. CalmHET hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity towards cultured CalmHET CALM-AF10 leukemia cells and this effect was additive to that of chemotherapy. In mice transplanted with CalmHET CALM-AF10 leukemia, we found that dietary iron restriction reduces tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CalmHET CALM-AF10 leukemia. In summary, while Calm heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients. PMID:25193880

AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

PubMed

Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

2015-08-21

AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties.

Efficacy and safety of rivaroxaban versus warfarin in patients from mainland China with nonvalvular atrial fibrillation: A subgroup analysis from the ROCKET AF trial.

PubMed

Sun, Yihong; Hu, Dayi; Stevens, Susanna; Lokhnygina, Yuliya; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Piccini, Jonathan P; Singer, Daniel E; Fox, Keith A A; Patel, Manesh R

2017-08-01

The ROCKET AF study evaluated once-daily rivaroxaban versus dose-adjusted warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). In this analysis, we compared rivaroxaban with warfarin in patients with AF from China, East Asia, and the rest of the world (ROW). We assessed baseline demographics and interaction of treatment effects of rivaroxaban versus warfarin among patients from mainland China, other East Asian countries, and ROW. Of the 14,236 patients enrolled in the per-protocol population, 495 were from mainland China, 433 from other East-Asian regions, and 13,308 from the rest of the world (ROW). At baseline, patients from China had significantly higher rates of previous stroke/transient ischemic attack (TIA) compared with patients from other East Asian regions and ROW (79.6%, 44.6%, 51.6% respectively; p<0.0001) and lower rates of VKA use (33.7%, 66.7%, 63.4%, respectively; p<0.0001). The rates of stroke or systemic embolism among those on warfarin while on treatment was 5.23% in patients from China, 1.82% in those from other East Asian regions, and 2.07% from ROW; on rivaroxaban, the rates were 2.29% in patients from China, 1.86% in those from other east Asian regions, and 1.67% from ROW. There were no significant treatment-by-region interactions for any efficacy or safety outcome (all p>0.12). Numerically higher rates of intracranial bleeding were seen in patients from China receiving warfarin versus rivaroxaban. In patients from China, rates of intracranial hemorrhage were numerically lower among those receiving rivaroxaban and consistent with the overall trial. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767. Copyright © 2017 Elsevier Ltd. All rights reserved.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial.

PubMed

Kotecha, Dipak; Calvert, Melanie; Deeks, Jonathan J; Griffith, Michael; Kirchhof, Paulus; Lip, Gregory Yh; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-07-20

Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications

Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial.

PubMed

Vranckx, Pascal; Lewalter, Thorsten; Valgimigli, Marco; Tijssen, Jan G; Reimitz, Paul-Egbert; Eckardt, Lars; Lanz, Hans-Joachim; Zierhut, Wolfgang; Smolnik, Rüdiger; Goette, Andreas

2018-02-01

The optimal antithrombotic treatment after percutaneous coronary intervention (PCI) with stenting in patients with atrial fibrillation (AF) is unknown. In the ENGAGE AF-TIMI 48 trial, edoxaban was noninferior to a vitamin K antagonist (VKA) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF. The effects of edoxaban in combination with single- or dual-antiplatelet therapy in the setting of PCI are unexplored. The ENTRUST-AF PCI trial is a multinational, multicenter, randomized, open-label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF. Patients are randomized between 4 hours and 5 days after successful PCI to either an edoxaban-based strategy (experimental arm; 60 mg [or 30 mg according to dose reduction criteria] once daily plus a P2Y 12 antagonist [default clopidogrel, 75 mg once daily] for 12 months) or a VKA-based strategy (control arm; VKA plus a P2Y 12 antagonist [as above] plus acetylsalicylic acid [100 mg once daily] for 30 days to 12 months). The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis-defined major or clinically relevant nonmajor bleeding. The main efficacy end point is the composite of cardiovascular death, stroke, systemic embolic events, spontaneous myocardial infarction, and definite stent thrombosis. The ENTRUST-AF PCI trial tests the hypothesis that an edoxaban-based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual-antiplatelet therapy in patients with AF in need of oral anticoagulation. The relative risk of ischemic events between groups will be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: the Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial).

PubMed

Bansilal, Sameer; Bloomgarden, Zachary; Halperin, Jonathan L; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Becker, Richard C; Breithardt, Günter; Hacke, Werner; Hankey, Graeme J; Nessel, Christopher C; Singer, Daniel E; Berkowitz, Scott D; Piccini, Jonathan P; Mahaffey, Kenneth W; Fox, Keith A A

2015-10-01

The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial. We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding. The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients. The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF. Copyright © 2015 The Authors. Published by Elsevier Inc. All

U2AF1 mutations alter splice site recognition in hematological malignancies.

PubMed

Ilagan, Janine O; Ramakrishnan, Aravind; Hayes, Brian; Murphy, Michele E; Zebari, Ahmad S; Bradley, Philip; Bradley, Robert K

2015-01-01

Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies. Here, we sought to determine how mutations affecting the 3' splice site recognition factor U2AF1 alter its normal role in RNA splicing. We find that U2AF1 mutations influence the similarity of splicing programs in leukemias, but do not give rise to widespread splicing failure. U2AF1 mutations cause differential splicing of hundreds of genes, affecting biological pathways such as DNA methylation (DNMT3B), X chromosome inactivation (H2AFY), the DNA damage response (ATR, FANCA), and apoptosis (CASP8). We show that U2AF1 mutations alter the preferred 3' splice site motif in patients, in cell culture, and in vitro. Mutations affecting the first and second zinc fingers give rise to different alterations in splice site preference and largely distinct downstream splicing programs. These allele-specific effects are consistent with a computationally predicted model of U2AF1 in complex with RNA. Our findings suggest that U2AF1 mutations contribute to pathogenesis by causing quantitative changes in splicing that affect diverse cellular pathways, and give insight into the normal function of U2AF1's zinc finger domains. © 2015 Ilagan et al.; Published by Cold Spring Harbor Laboratory Press.

Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial.

PubMed

Singer, Daniel E; Hellkamp, Anne S; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R; Piccini, Jonathan P; Hankey, Graeme J; Breithardt, Günter; Halperin, Jonathan L; Becker, Richard C; Hacke, Werner; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

2015-03-03

In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted. TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported. URL: ClinicalTrials.gov. Unique identifier: NCT00403767. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

PubMed Central

Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

2015-01-01

Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial

PubMed Central

Schregel, Katharina; Karch, André; Weber-Krueger, Mark; Stahrenberg, Raoul; Gröschel, Klaus; Knauth, Michael; Psychogios, Marios-Nikos; Wachter, Rolf; Liman, Jan

2017-01-01

Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65–3.79, p = 0.317), the short-term (OR 0.64, 0.26–1.58, p = 0.327) or long-term diagnosis of AF (OR 0.72, 0.31–1.68, p = 0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF. PMID:28536667

Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial.

PubMed

Maier, Ilko L; Schregel, Katharina; Karch, André; Weber-Krueger, Mark; Mikolajczyk, Rafael T; Stahrenberg, Raoul; Gröschel, Klaus; Bähr, Mathias; Knauth, Michael; Psychogios, Marios-Nikos; Wachter, Rolf; Liman, Jan

2017-01-01

Background . Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods . Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results . From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65-3.79, p = 0.317), the short-term (OR 0.64, 0.26-1.58, p = 0.327) or long-term diagnosis of AF (OR 0.72, 0.31-1.68, p = 0.448). Conclusions . This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.

AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

PubMed Central

Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

2015-01-01

AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).

PubMed

Washam, Jeffrey B; Stevens, Susanna R; Lokhnygina, Yuliya; Halperin, Jonathan L; Breithardt, Günter; Singer, Daniel E; Mahaffey, Kenneth W; Hankey, Graeme J; Berkowitz, Scott D; Nessel, Christopher C; Fox, Keith A A; Califf, Robert M; Piccini, Jonathan P; Patel, Manesh R

2015-06-13

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076). Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients

Current presentation and management of 7148 patients with atrial fibrillation in cardiology and internal medicine hospital centers: the ATA AF study.

PubMed

Di Pasquale, Giuseppe; Mathieu, Giovanni; Maggioni, Aldo Pietro; Fabbri, Gianna; Lucci, Donata; Vescovo, Giorgio; Pirelli, Salvatore; Chiarella, Francesco; Scherillo, Marino; Gulizia, Michele Massimo; Gussoni, Gualberto; Colombo, Fabrizio; Panuccio, Domenico; Nozzoli, Carlo; Berisso, Massimo Zoni

2013-09-10

Atrial fibrillation (AF) is associated with a high risk of stroke and mortality. To describe the difference in AF management of patients (pts) referred to Cardiology (CARD) or Internal Medicine (MED) units in Italy. From May to July 2010, 360 centers enrolled 7148 pts (54% in CARD and 46% in MED). Median age was 77 years (IQR 70-83). Hypertension was the most prevalent associated condition, followed by hypercholesterolemia (28.9%), heart failure (27.7%) and diabetes (24.3%). MED pts were older, more frequently females and more often with comorbidities than CARD pts. In the 4845 pts with nonvalvular AF, a CHADS2 score ≥ 2 was present in 53.0% of CARD vs 75.3% of MED pts (p<.0001). Oral anticoagulants (OAC) were prescribed in 64.2% of CARD vs 46.3% of MED pts (p<.0001); OAC prescription rate was 49.6% in CHADS2 0 and 56.2% in CHADS2 score ≥ 2 pts. At the adjusted analysis patients managed in MED had a significantly lower probability to be treated with OAC. Rate control strategy was pursued in 51.4% of the pts (60.5% in MED and 43.6% in CARD) while rhythm control was the choice in 39.8% of CARD vs 12.9% of MED pts (p<.0001). Cardiologists and internists seem to manage pts with large epidemiological differences. Both CARD and MED specialists currently fail to prescribe OAC in accordance with stroke risk. Patients managed by MED specialists have a lower probability to receive an OAC treatment, irrespective of the severity of clinical conditions. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Biomarkers in Persistent AF and Heart Failure: Impact of Catheter Ablation Compared with Rate Control.

PubMed

Jones, David G; Haldar, Shouvik K; Donovan, Jacqueline; McDonagh, Theresa A; Sharma, Rakesh; Hussain, Wajid; Markides, Vias; Wong, Tom

2016-09-01

To investigate the effects of catheter ablation and rate control strategies on cardiac and inflammatory biomarkers in patients with heart failure and persistent atrial fibrillation (AF). Patients were recruited from the ARC-HF trial (catheter Ablation vs Rate Control for management of persistent AF in Heart Failure, NCT00878384), which compared ablation with rate control for persistent AF in heart failure. B-type natriuretic peptide (BNP), midregional proatrial natriuretic peptide (MR-proANP), apelin, and interleukin-6 (IL-6) were assayed at baseline, 3 months, 6 months, and 12 months. The primary end point, analyzed per-protocol, was changed from baseline at 12 months. Of 52 recruited patients, 24 ablation and 25 rate control subjects were followed to 12 months. After 1.2 ± 0.5 procedures, sinus rhythm was present in 22 (92%) ablation patients; under rate control, rate criteria were achieved in 23 (96%) of 24 patients remaining in AF. At 12 months, MR-proANP fell significantly in the ablation arm (-106.0 pmol/L, interquartile range [IQR] -228.2 to -60.6) compared with rate control (-28.7 pmol/L, IQR -69 to +9.5, P = 0.028). BNP showed a similar trend toward reduction (P = 0.051), with no significant difference in apelin (P = 0.13) or IL-6 (P = 0.68). Changes in MR-proANP and BNP correlated with peak VO2 and ejection fraction, and MR-proANP additionally with quality-of-life score. Catheter ablation, compared with rate control, in patients with heart failure and persistent AF was associated with significant reduction in MR-proANP, which correlated with physiological and symptomatic improvement. Ablation-based rhythm control may induce beneficial cardiac remodeling, unrelated to changes in inflammatory state. This may have prognostic implications, which require confirmation by event end point studies. © 2016 Wiley Periodicals, Inc.

Quality of life assessment in the randomized PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial of patients at risk for stroke with nonvalvular atrial fibrillation.

PubMed

Alli, Oluseun; Doshi, Shepal; Kar, Saibal; Reddy, Vivek; Sievert, Horst; Mullin, Chris; Swarup, Vijay; Whisenant, Brian; Holmes, David

2013-04-30

This study sought to assess quality of life parameters in a subset of patients enrolled in the PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial. The PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) and CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, and prior stroke, transient ischemic attack, or thromboembolism) score ≥1, a left atrial appendage closure device is noninferior to long-term warfarin for stroke prevention. Given this equivalency, quality of life (QOL) indicators are an important metric for evaluating these 2 different strategies. QOL using the Short-Form 12 Health Survey, version 2, measurement tool was obtained at baseline and 12 months in a subset of 547 patients in the PROTECT AF trial (361 device and 186 warfarin patients). The analysis cohort consisted of patients for whom either paired quality of life data were available after 12 months of follow-up or for patients who died. With the device, the total physical score improved in 34.9% and was unchanged in 29.9% versus warfarin in whom 24.7% were improved and 31.7% were unchanged (p = 0.01). Mental health improvement occurred in 33.0% of the device group versus 22.6% in the warfarin group (p = 0.06). There was a significant improvement in QOL in patients randomized to device for total physical score, physical function, and in physical role limitation compared to control. There were significant differences in the change in total physical score among warfarin naive and not-warfarin naive subgroups in the device group compared to control, but larger gains were seen with the warfarin naive subgroup with a 12-month change of 1.3 ± 8.8 versus -3.6 ± 6.7 (p = 0.0004) device compared to warfarin

Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation: The REHEARSE-AF Study.

PubMed

Halcox, Julian P J; Wareham, Kathie; Cardew, Antonia; Gilmore, Mark; Barry, James P; Phillips, Ceri; Gravenor, Michael B

2017-11-07

Asymptomatic atrial fibrillation (AF) is increasingly common in the aging population and implicated in many ischemic strokes. Earlier identification of AF with appropriate anticoagulation may decrease stroke morbidity and mortality. We conducted a randomized controlled trial of AF screening using an AliveCor Kardia monitor attached to a WiFi-enabled iPod to obtain ECGs (iECGs) in ambulatory patients. Patients ≥65 years of age with a CHADS-VASc score ≥2 free from AF were randomized to the iECG arm or routine care (RC). iECG participants acquired iECGs twice weekly over 12 months (plus additional iECGs if symptomatic) onto a secure study server with overread by an automated AF detection algorithm and by a cardiac physiologist and/or consultant cardiologist. Time to diagnosis of AF was the primary outcome measure. The overall cost of the devices, ECG interpretation, and patient management were captured and used to generate the cost per AF diagnosis in iECG patients. Clinical events and patient attitudes/experience were also evaluated. We studied 1001 patients (500 iECG, 501 RC) who were 72.6±5.4 years of age; 534 were female. Mean CHADS-VASc score was 3.0 (heart failure, 1.4%; hypertension, 54%; diabetes mellitus, 30%; prior stroke/transient ischemic attack, 6.5%; arterial disease, 15.9%; all CHADS-VASc risk factors were evenly distributed between groups). Nineteen patients in the iECG group were diagnosed with AF over the 12-month study period versus 5 in the RC arm (hazard ratio, 3.9; 95% confidence interval=1.4-10.4; P =0.007) at a cost per AF diagnosis of $10 780 (£8255). There was a similar number of stroke/transient ischemic attack/systemic embolic events (6 versus 10, iECG versus RC; hazard ratio=0.61; 95% confidence interval=0.22-1.69; P =0.34). The majority of iECG patients were satisfied with the device, finding it easy to use without restricting activities or causing anxiety. Screening with twice-weekly single-lead iECG with remote interpretation in

Study design of J-ELD AF: A multicenter prospective cohort study to investigate the efficacy and safety of apixaban in Japanese elderly patients.

PubMed

Akao, Masaharu; Yamashita, Takeshi; Okumura, Ken

2016-12-01

Apixaban, one of the non-vitamin K antagonist oral anticoagulants, was reported to be effective and safe in stroke prevention in patients with atrial fibrillation (AF) based on the global randomized clinical trial, but data are limited on the efficacy and safety of apixaban in Japanese elderly patients. The J-ELD AF Registry is a large-scale, contemporary observational study, continuously and prospectively registering elderly Japanese patients with AF aged 75 years or older who are currently taking apixaban or the elderly who are to receive apixaban in daily clinical practice, and accumulating the outcomes during one-year follow-up period. In addition to standard baseline characteristics, prothrombin time and anti-Xa activity will be measured to investigate the biomarker characteristics. The primary efficacy endpoints will be stroke and systemic embolism, and the primary safety endpoint will be major bleeding requiring hospitalization. The secondary endpoints in this study will be all-cause death, cardiovascular death, acute myocardial infarction, and the composite of stroke/systemic embolism, cardiovascular death, and acute myocardial infarction. As a primary analysis, the primary/secondary endpoints in the enrolled patients will be totalized for the entire group, and the incidence of events will be described by age, CHADS 2 score, HAS-BLED score, and apixaban dose (5 or 2.5mg bid). The factors that independently predict the incidence of the primary/secondary endpoints will be searched for by Cox regression. The relationship between the biomarkers and the primary/secondary endpoints will also be examined in an explorative manner. This study will provide important information on the efficacy and safety of apixaban in elderly Japanese patients aged 75 years or older, and those of low-dose administration of apixaban (2.5mg bid) for which many of the Japanese elderly are indicated. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights

A Critical Role for CRM1 in Regulating HOXA Gene Transcription in CALM-AF10 Leukemias

PubMed Central

Conway, Amanda E.; Haldeman, Jonathan M.; Wechsler, Daniel S.; Lavau, Catherine P.

2014-01-01

The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor. PMID:25027513

Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial.

PubMed

Kato, Eri Toda; Giugliano, Robert P; Ruff, Christian T; Koretsune, Yukihiro; Yamashita, Takeshi; Kiss, Robert Gabor; Nordio, Francesco; Murphy, Sabina A; Kimura, Tetsuya; Jin, James; Lanz, Hans; Mercuri, Michele; Braunwald, Eugene; Antman, Elliott M

2016-05-20

Elderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF-TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age. Twenty-one thousand one-hundred and five patients enrolled in the ENGAGE AF-TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P<0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups (Ptrend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66-1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70-0.99]). The absolute risk difference in major bleeding (-82 events/10 000 pt-yrs) and in intracranial hemorrhage (-73 events/10 000 pt-yrs) both favored edoxaban over warfarin in older patients. Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene

PubMed Central

Catalina, Purificación; Rodríguez, René; Melen, Gustavo J.; Bueno, Clara; Arriero, Mar; García-Sánchez, Félix; Lassaletta, Alvaro; García-Sanz, Ramón

2009-01-01

MLL-AF4 fusion is a hallmark genetic abnormality in infant B-acute lymphoblastic leukemia (B-ALL) known to arise in utero. The cellular origin of leukemic fusion genes during human development is difficult to ascertain. The bone marrow (BM) microenvironment plays an important role in the pathogenesis of several hematological malignances. BM mesenchymal stem cells (BM-MSC) from 38 children diagnosed with cytogenetically different acute leukemias were screened for leukemic fusion genes. Fusion genes were absent in BM-MSCs of childhood leukemias carrying TEL-AML1, BCR-ABL, AML1-ETO, MLL-AF9, MLL-AF10, MLL-ENL or hyperdiploidy. However, MLL-AF4 was detected and expressed in BM-MSCs from all cases of MLL-AF4+ B-ALL. Unlike leukemic blasts, MLL-AF4+ BM-MSCs did not display monoclonal Ig gene rearrangements. Endogenous or ectopic expression of MLL-AF4 exerted no effect on MSC culture homeostasis. These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4+ B-ALL. MLL-AF4 itself is not sufficient for MSC transformation and the expression of MLL-AF4 in MSCs is compatible with a mesenchymal phenotype, suggesting a differential impact in the hematopoietic system and mesenchyme. The absence of monoclonal rearrangements in MLL-AF4+ BM-MSCs precludes the possibility of cellular plasticity or de-differentiation of B-ALL blasts and suggests that MLL-AF4 might arise in a population of prehematopoietic precursors. PMID:19995953

Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice

PubMed Central

Shah, Rohan; Patel, Manesh R.

2016-01-01

Background: The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. Methods: The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Results: Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Conclusions: Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely

Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice.

PubMed

Shah, Rohan; Patel, Manesh R

2017-03-01

The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical

Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

PubMed

Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

2016-01-01

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. Copyright © 2016 Elsevier Inc. All rights reserved.

Stability of rotors and focal sources for human atrial fibrillation: focal impulse and rotor mapping (FIRM) of AF sources and fibrillatory conduction.

PubMed

Swarup, Vijay; Baykaner, Tina; Rostamian, Armand; Daubert, James P; Hummel, John; Krummen, David E; Trikha, Rishi; Miller, John M; Tomassoni, Gery F; Narayan, Sanjiv M

2014-12-01

Several groups report electrical rotors or focal sources that sustain atrial fibrillation (AF) after it has been triggered. However, it is difficult to separate stable from unstable activity in prior studies that examined only seconds of AF. We applied phase-based focal impulse and rotor mapping (FIRM) to study the dynamics of rotors/sources in human AF over prolonged periods of time. We prospectively mapped AF in 260 patients (169 persistent, 61 ± 12 years) at 6 centers in the FIRM registry, using baskets with 64 contact electrodes per atrium. AF was phase mapped (RhythmView, Topera, Menlo Park, CA, USA). AF propagation movies were interpreted by each operator to assess the source stability/dynamics over tens of minutes before ablation. Sources were identified in 258 of 260 of patients (99%), for 2.8 ± 1.4 sources/patient (1.8 ± 1.1 in left, 1.1 ± 0.8 in right atria). While AF sources precessed in stable regions, emanating activity including spiral waves varied from collision/fusion (fibrillatory conduction). Each source lay in stable atrial regions for 4,196 ± 6,360 cycles, with no differences between paroxysmal versus persistent AF (4,290 ± 5,847 vs. 4,150 ± 6,604; P = 0.78), or right versus left atrial sources (P = 0.26). Rotors and focal sources for human AF mapped by FIRM over prolonged time periods precess ("wobble") but remain within stable regions for thousands of cycles. Conversely, emanating activity such as spiral waves disorganize and collide with the fibrillatory milieu, explaining difficulties in using activation mapping or signal processing analyses at fixed electrodes to detect AF rotors. These results provide a rationale for targeted ablation at AF sources rather than fibrillatory spiral waves. © 2014 Wiley Periodicals, Inc.

STBC AF relay for unmanned aircraft system

NASA Astrophysics Data System (ADS)

Adachi, Fumiyuki; Miyazaki, Hiroyuki; Endo, Chikara

2015-01-01

If a large scale disaster similar to the Great East Japan Earthquake 2011 happens, some areas may be isolated from the communications network. Recently, unmanned aircraft system (UAS) based wireless relay communication has been attracting much attention since it is able to quickly re-establish the connection between isolated areas and the network. However, the channel between ground station (GS) and unmanned aircraft (UA) is unreliable due to UA's swing motion and as consequence, the relay communication quality degrades. In this paper, we introduce space-time block coded (STBC) amplify-and-forward (AF) relay for UAS based wireless relay communication to improve relay communication quality. A group of UAs forms single frequency network (SFN) to perform STBC-AF cooperative relay. In STBC-AF relay, only conjugate operation, block exchange and amplifying are required at UAs. Therefore, STBC-AF relay improves the relay communication quality while alleviating the complexity problem at UAs. It is shown by computer simulation that STBC-AF relay can achieve better throughput performance than conventional AF relay.

Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

PubMed

Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

2016-10-04

To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

AF Sites

Science.gov Websites

Speeches Archive Former AF Top 3 Viewpoints and Speeches Air Force Warrior Games 2017 Events 2018 Air Force Strategic Documents Desert Storm 25th Anniversary Observances DoD Warrior Games Portraits in Courage

AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson's disease

PubMed Central

Haskin, Joseph; Szargel, Raymonde; Shani, Vered; Mekies, Lucy N.; Rott, Ruth; Lim, Grace G. Y.; Lim, Kah-Leong; Bandopadhyay, Rina; Wolosker, Herman; Engelender, Simone

2013-01-01

Parkin E3 ubiquitin-ligase activity and its role in mitochondria homeostasis are thought to play a role in Parkinson's disease (PD). We now report that AF-6 is a novel parkin interacting protein that modulates parkin ubiquitin-ligase activity and mitochondrial roles. Parkin interacts with the AF-6 PDZ region through its C-terminus. This leads to ubiquitination of cytosolic AF-6 and its degradation by the proteasome. On the other hand, endogenous AF-6 robustly increases parkin translocation and ubiquitin-ligase activity at the mitochondria. Mitochondrial AF-6 is not a parkin substrate, but rather co-localizes with parkin and enhances mitochondria degradation through PINK1/parkin-mediated mitophagy. On the other hand, several parkin and PINK1 juvenile disease-mutants are insensitive to AF-6 effects. AF-6 is present in Lewy bodies and its soluble levels are strikingly decreased in the caudate/putamen and substantia nigra of sporadic PD patients, suggesting that decreased AF-6 levels may contribute to the accumulation of dysfunctional mitochondria in the disease. The identification of AF-6 as a positive modulator of parkin translocation to the mitochondria sheds light on the mechanisms involved in PD and underscores AF-6 as a novel target for future therapeutics. PMID:23393160

Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial.

PubMed

Piccini, Jonathan P; Garg, Jyotsna; Patel, Manesh R; Lokhnygina, Yuliya; Goodman, Shaun G; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Nessel, Christopher C; Mahaffey, Kenneth W; Singer, Daniel E; Califf, Robert M; Fox, Keith A A

2014-07-21

There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors. Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P < 0.0001]. Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non-central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin; HR 0.89; 95% CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin; HR 0.69, 95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin (interaction P = 0.51 and 0.11). Among high-risk patients with atrial fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Medical cost reductions associated with the usage of novel oral anticoagulants vs warfarin among atrial fibrillation patients, based on the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Deitelzweig, Steve; Amin, Alpesh; Jing, Yonghua; Makenbaeva, Dinara; Wiederkehr, Daniel; Lin, Jay; Graham, John

2012-01-01

The randomized clinical trials, RE-LY, ROCKET-AF, and ARISTOTLE, demonstrate that the novel oral anticoagulants (NOACs) are effective options for stroke prevention among non-valvular atrial fibrillation (AF) patients. This study aimed to evaluate the medical cost reductions associated with the use of individual NOACs instead of warfarin from the US payer perspective. Rates for efficacy and safety clinical events for warfarin were estimated as the weighted averages from the RE-LY, ROCKET-AF and ARISTOTLE trials, and event rates for NOACs were determined by applying trial hazard ratios or relative risk ratios to such weighted averages. Incremental medical costs to a US health payer of an AF patient experiencing a clinical event during 1 year following the event were obtained from published literature and inflation adjusted to 2010 cost levels. Medical costs, excluding drug costs, were evaluated and compared for each NOAC vs warfarin. Sensitivity analyses were conducted to determine the influence of variations in clinical event rates and incremental costs on the medical cost reduction. In a patient year, the medical cost reduction associated with NOAC usage instead of warfarin was estimated to be -$179, -$89, and -$485 for dabigatran, rivaroxaban, and apixaban, respectively. When clinical event rates and costs were allowed to vary simultaneously, through a Monte Carlo simulation, the 95% confidence interval of annual medical costs differences ranged between -$424 and +$71 for dabigatran, -$301 and +$135 for rivaroxaban, and -$741 and -$252 for apixaban, with a negative number indicating a cost reduction. Of the 10,000 Monte-Carlo iterations 92.6%, 79.8%, and 100.0% were associated with a medical cost reduction >$0 for dabigatran, rivaroxaban, and apixaban, respectively. Usage of the NOACs, dabigatran, rivaroxaban, and apixaban may be associated with lower medical (excluding drug costs) costs relative to warfarin, with apixaban having the most substantial medical cost

Yield of atrial fibrillation detection with Textile Wearable Holter from the acute phase of stroke: Pilot study of Crypto-AF registry.

PubMed

Pagola, Jorge; Juega, Jesus; Francisco-Pascual, Jaume; Moya, Angel; Sanchis, Mireia; Bustamante, Alejandro; Penalba, Anna; Usero, Maria; Cortijo, Elisa; Arenillas, Juan F; Calleja, Ana I; Sandin-Fuentes, Maria; Rubio, Jeronimo; Mancha, Fernando; Escudero-Martinez, Irene; Moniche, Francisco; de Torres, Reyes; Pérez-Sánchez, Soledad; González-Matos, Carlos E; Vega, Ángela; Pedrote, Alonso A; Arana-Rueda, Eduardo; Montaner, Joan; Molina, Carlos A

2018-01-15

We describe the feasibility of monitoring with a Textile Wearable Holter (TWH) in patients included in Crypto AF registry. We monitored cryptogenic stroke patients from stroke onset (<3days) continuously during 28days. We employed a TWH composed by a garment and a recorder. We compared two garments (Lead and Vest) to assess rate of undiagnosed Atrial Fibrillation (AF) detection, monitoring compliance, comfortability (1 to 5 points), skin lesions, and time analyzed. We describe the timing of AF detection in three periods (0-3, 4-15 and 16-28days). The rate of undiagnosed AF detection with TWH was 21.9% (32 out of 146 patients who completed the monitoring). Global time compliance was 90% of the time expected (583/644h). The level of comfortability was 4 points (IQR 3-5). We detected reversible skin lesions in 5.47% (8/146). The comfortability was similar but time compliance (in hours) was longer in Vest group 591 (IQR [521-639]) vs. Lead 566 (IQR [397-620]) (p=0.025). Also, time analyzed was more prolonged in Vest group 497 (IQR [419-557]) vs. Lead (336h (IQR [140-520]) (p=0.001)). The incidence of AF increases from 5.6% (at 3days) to 17.5% (at 15th day) and up to 20.9% (at 28th day). The percentage of AF episodes detected only in each period was 12.5% (0-3days); 21.7% (4-15days) and 19% (16-28days). 28days Holter monitoring from the acute phase of the stroke was feasible with TWH. Following our protocol, only five patients were needed to screen to detected one case of AF. Copyright © 2017 Elsevier B.V. All rights reserved.

AF-Shell 1.0 User Guide

NASA Technical Reports Server (NTRS)

McElroy, Mark W.

2017-01-01

This document serves as a user guide for the AF-Shell 1.0 software, an efficient tool for progressive damage simulation in composite laminates. This guide contains minimal technical material and is meant solely as a guide for a new user to apply AF-Shell 1.0 to laminate damage simulation problems.

Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

PubMed Central

Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

2016-01-01

We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

AF-GEOSpace Version 2.1 Release

NASA Astrophysics Data System (ADS)

Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Perry, K. L.; Tautz, M.; Roth, C.

2006-05-01

AF-GEOSpace Version 2.1 is a graphics-intensive software program with space environment models and applications developed recently by the Space Weather Center of Excellence at AFRL. A review of new and planned AF-GEOSpace capabilities will be given. The software addresses a wide range of physical domains and addresses such topics as solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; determination of link outage regions for active ionospheric conditions; satellite magnetic conjugate studies, scientific model validation and comparison, physics research, and education. Previously, Version 2.0 provided a simplified graphical user interface, improved science and application modules, significantly enhanced graphical performance, common input data archive sets, and 1-D, 2-D, and 3- D visualization tools for all models. Dynamic capabilities permit multiple environments to be generated at user- specified time intervals while animation tools enable the display of satellite orbits and environment data together as a function of time. Building on the Version 2.0 software architecture, AF-GEOSpace Version 2.1 includes a host of new modules providing, for example, plasma sheet charged particle fluxes, neutral atmosphere densities, 3-D cosmic ray cutoff maps, low-altitude trapped proton belt flux specification, DMSP particle data displays, satellite magnetic field footprint mapping determination, and meteor sky maps and shower/storm fluxes with spacecraft impact probabilities. AF-GEOSpace Version 2.1 was

Impact of acute atrial fibrillation termination and prolongation of atrial fibrillation cycle length on the outcome of ablation of persistent atrial fibrillation: A substudy of the STAR AF II trial.

PubMed

Kochhäuser, Simon; Jiang, Chen-Yang; Betts, Timothy R; Chen, Jian; Deisenhofer, Isabel; Mantovan, Roberto; Macle, Laurent; Morillo, Carlos A; Haverkamp, Wilhelm; Weerasooriya, Rukshen; Albenque, Jean-Paul; Nardi, Stefano; Menardi, Endrj; Novak, Paul; Sanders, Prashanthan; Verma, Atul

2017-04-01

Controversy exists about the impact of acute atrial fibrillation (AF) termination and prolongation of atrial fibrillation cycle length (AFCL) during ablation on long-term procedural outcome. The purpose of this study was to analyze the influence of AF termination and AFCL prolongation on freedom from AF in patients from the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II) trial. Acute changes in AFCL and AF termination were collected during the index procedure of the STAR AF II trial and compared to recurrence of AF at 18 months. Recurrence was assessed by ECG, Holter (3, 6, 9, 12, 18 months), and weekly transtelephonic ECG monitoring for 18 months. AF terminated in 8% of the pulmonary vein isolation (PVI) arm, 45% in the PVI+complex electrogram arm, and 22% of the PVI+linear ablation arm (P <.001), but freedom from AF did not differ among the 3 groups (P = .15). Freedom from AF was significantly higher in patients who presented to the laboratory in sinus rhythm (SR) compared to those without AF termination (63% vs 44%, P = .007). Patients with AF termination had an intermediate outcome (53%) that was not significantly different from those in SR (P = .84) or those who did not terminate (P = .08). AF termination was a univariable predictor of success (P = .007), but by multivariable analysis, presence of early SR was the strongest predictor of success (hazard ratio 0.67, P = .004). Prolongation of AFCL was not predictive of 18-month freedom from AF. Acute AF termination and prolongation in AFCL did not consistently predict 18-month freedom from AF. Presence of SR before or early during the ablation was the strongest predictor of better outcome. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Time trends in antithrombotic management of patients with atrial fibrillation treated with coronary stents: Results from TALENT-AF (The internAtionaL stENT - Atrial Fibrillation study) multicenter registry.

PubMed

Potter, Brian J; Andò, Giuseppe; Cimmino, Giovanni; Ladeiras-Lopes, Ricardo; Frikah, Zied; Chen, Xin Yue; Virga, Vittorio; Goncalves-Almeida, Joao; Camm, A John; Fox, Keith A A

2018-04-01

Antithrombotic management of patients with atrial fibrillation (AF) requiring percutaneous coronary intervention (PCI) is highly variable; limited evidence-based guidelines exist to influence practice. Patient characteristics and availability of novel drugs may have contributed to practice variability. We undertook an international multicenter retrospective registry of AF patients treated with PCI. The primary measures of interest were antiplatelet and OAC prescriptions at discharge. We compared temporal trends between Prior (2010-2012) and Recent (2013-2015) cohorts and investigated variables associated with OAC prescription. We identified 488 cases (140 Prior, 348 Recent). Median CHADS 2 and HAS-BLED scores were 2 (IQR, 1-3) and 2 (IQR, 2-3). Clinical characteristics were similar between cohorts, with high (85%) prevalence of ACS. More patients in the Recent cohort, compared with Prior, received OAC (56.9% vs 44.3%; P = 0.01) and NOAC (27.3% vs 3.6%; P < 0.01) at baseline. Triple therapy at discharge was not different between the cohorts. Clinical presentation with ACS and consequent use of potent P2Y 12 inhibitors were associated with reduced odds of OAC prescription at discharge (OR: 0.57, P = 0.045 and OR: 0.38, P = 0.023, respectively). Despite little change over time in clinical characteristics of AF patients undergoing PCI, significantly more patients received OAC at presentation. However, triple therapy was not more frequent in the Recent cohort, and ACS presentation was associated with lack of OAC at discharge. We underscore the need for trial evidence and use of updated guidelines to assist clinicians in balancing ischemic and bleeding risks. © 2018 Wiley Periodicals, Inc.

Identification of U2AF(35)-dependent exons by RNA-Seq reveals a link between 3′ splice-site organization and activity of U2AF-related proteins

PubMed Central

Kralovicova, Jana; Knut, Marcin; Cross, Nicholas C. P.; Vorechovsky, Igor

2015-01-01

The auxiliary factor of U2 small nuclear RNA (U2AF) is a heterodimer consisting of 65- and 35-kD proteins that bind the polypyrimidine tract (PPT) and AG dinucleotides at the 3′ splice site (3′ss). The gene encoding U2AF35 (U2AF1) is alternatively spliced, giving rise to two isoforms U2AF35a and U2AF35b. Here, we knocked down U2AF35 and each isoform and characterized transcriptomes of HEK293 cells with varying U2AF35/U2AF65 and U2AF35a/b ratios. Depletion of both isoforms preferentially modified alternative RNA processing events without widespread failure to recognize 3′ss or constitutive exons. Over a third of differentially used exons were terminal, resulting largely from the use of known alternative polyadenylation (APA) sites. Intronic APA sites activated in depleted cultures were mostly proximal whereas tandem 3′UTR APA was biased toward distal sites. Exons upregulated in depleted cells were preceded by longer AG exclusion zones and PPTs than downregulated or control exons and were largely activated by PUF60 and repressed by CAPERα. The U2AF(35) repression and activation was associated with a significant interchange in the average probabilities to form single-stranded RNA in the optimal PPT and branch site locations and sequences further upstream. Although most differentially used exons were responsive to both U2AF subunits and their inclusion correlated with U2AF levels, a small number of transcripts exhibited distinct responses to U2AF35a and U2AF35b, supporting the existence of isoform-specific interactions. These results provide new insights into function of U2AF and U2AF35 in alternative RNA processing. PMID:25779042

Is AF Ablation Cost Effective?

PubMed Central

Martin-Doyle, William; Reynolds, Matthew R.

2010-01-01

The use of catheter ablation to treat AF is increasing rapidly, but there is presently an incomplete understanding of its cost-effectiveness. AF ablation procedures involve significant up-front expenditures, but multiple randomized trials have demonstrated that ablation is more effective than antiarrhythmic drugs at maintaining sinus rhythm in a second-line and possibly first-line rhythm control setting. Although truly long-term data are limited, ablation, as compared with antiarrrhythmic drugs, also appears associated with improved symptoms and quality of life and a reduction in downstream hospitalization and other health care resource utilization. Several groups have developed cost effectiveness models comparing AF ablation primarily to antiarrhythmic drugs and the model results suggest that ablation likely falls within the range generally accepted as cost-effective in developed nations. This paper will review available information on the cost-effectiveness of catheter ablation for the treatment of atrial fibrillation, and discuss continued areas of uncertainty where further research is required. PMID:20936083

Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.

PubMed

Parra Lopez, Rafael; Nemes, Laszlo; Jimenez-Yuste, Victor; Rusen, Luminita; Cid, Ana R; Charnigo, Robert J; Baumann, James A; Smith, Lynne; Korth-Bradley, Joan M; Rendo, Pablo

2015-10-01

This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).

AF-GEOSPACE Version 2.1

NASA Astrophysics Data System (ADS)

Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Tautz, M.; Roth, C.

2004-05-01

AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed and distributed by the Space Weather Center of Excellence at AFRL. A review of current (Version 2.0) and planned (Version 2.1) AF-GEOSpace capabilities will be given. A wide range of physical domains is represented enabling the software to address such things as solar disturbance propagation, radiation belt configuration, and ionospheric auroral particle precipitation and scintillation. The software is currently being used to aid with the design, operation, and simulation of a wide variety of communications, navigation, and surveillance systems. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; scientific model validation and comparison, physics research, and education. Version 2.0 provided a simplified graphical user interface, improved science and application modules, and significantly enhanced graphical performance. Common input data archive sets, application modules, and 1-D, 2-D, and 3-D visualization tools are provided to all models. Dynamic capabilities permit multiple environments to be generated at user-specified time intervals while animation tools enable displays such as satellite orbits and environment data together as a function of time. Building on the existing Version 2.0 software architecture, AF-GEOSpace Version 2.1 is currently under development and will include a host of new modules to provide, for example, geosynchronous charged particle fluxes, neutral atmosphere densities

Impact of B-Type Natriuretic Peptide Level on Risk Stratification of Thromboembolism and Death in Patients With Nonvalvular Atrial Fibrillation　- The Hokuriku-Plus AF Registry.

PubMed

Hayashi, Kenshi; Tsuda, Toyonobu; Nomura, Akihiro; Fujino, Noboru; Nohara, Atsushi; Sakata, Kenji; Konno, Tetsuo; Nakanishi, Chiaki; Tada, Hayato; Nagata, Yoji; Teramoto, Ryota; Tanaka, Yoshihiro; Kawashiri, Masa-Aki; Yamagishi, Masakazu

2018-04-25

B-type natriuretic peptide (BNP) may be a predictor of stroke risk in patients with nonvalvular atrial fibrillation (NVAF); because heart failure is associated with the incidence of stroke in AF patients. However, limited data exist regarding the association between BNP at baseline and risks of thromboembolic events (TE) and death in NVAF patients. We prospectively studied 1,013 NVAF patients (725 men, 72.8±9.7 years old) from the Hokuriku-plus AF Registry to determine the relationship between BNP at baseline and prognosis among Japanese NVAF patients. During the follow-up period (median, 751 days); 31 patients experienced TE and there were 81 cases of TE/all-cause death. For each endpoint we constructed receiver-operating characteristic curves that gave cutoff points of BNP for TE (170 pg/mL) and TE/all-cause death (147 pg/mL). Multivariate analysis with the Cox-proportional hazards model indicated that high BNP was significantly associated with risks of TE (hazard ratio [HR] 3.86; 95% confidence interval [CI] 1.83-8.67; P=0.0003) and TE/all-cause death (HR 2.27; 95% CI 1.45-3.56; P=0.0003). Based on the C-index and net reclassification improvement, the addition of BNP to CHA 2 DS 2 -VASc statistically improved the prediction of TE. In a real-world cohort of Japanese NVAF patients, high BNP was significantly associated with TE and death. Plasma BNP might be a useful biomarker for these adverse clinical events.

Spotlight on unmet needs in stroke prevention: The PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials.

PubMed

Hemmrich, Melanie; Peterson, Eric D; Thomitzek, Karen; Weitz, Jeffrey I

2016-09-28

Atrial fibrillation (AF) is a major healthcare concern, being associated with an estimated five-fold risk of ischaemic stroke. In patients with AF, anticoagulants reduce stroke risk to a greater extent than acetylsalicylic acid (ASA) or dual antiplatelet therapy (DAPT) with ASA plus clopidogrel. Non-vitamin K antagonist oral anticoagulants (NOACs) are now a widely-accepted therapeutic option for stroke prevention in non-valvular AF (NVAF). There are particular patient types with NVAF for whom treatment challenges remain, owing to sparse clinical data, their high-risk nature or a need to harmonise anticoagulant and antiplatelet regimens if co-administered. This article focuses on three randomised controlled trials (RCTs) that are investigating the utility of rivaroxaban, a direct, oral, factor Xa inhibitor, in additional areas of stroke prevention where data for anticoagulants are lacking: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment (PIONEER AF-PCI); New Approach riVaroxoban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS); and Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO). Data from these studies present collaborative efforts to build upon existing registrational Phase III data for rivaroxaban, driving the need for effective and safe treatment of a wider range of patients for stroke prevention.

Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial).

PubMed

Washam, Jeffrey B; Hellkamp, Anne S; Lokhnygina, Yuliya; Piccini, Jonathan P; Berkowitz, Scott D; Nessel, Christopher C; Becker, Richard C; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Singer, Daniel E; Patel, Manesh R

2017-08-15

Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS 2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF. Copyright © 2017

The association between atrial fibrillation and cognitive function in patients with heart failure.

PubMed

Yang, Huifeng; Niu, Weihua; Zang, Xiaoying; Lin, Mei; Zhao, Yue

2017-02-01

Atrial fibrillation (AF) is associated with cognitive impairment in heart failure (HF). The purpose of this study was to examine whether AF independently predicted cognitive function in HF patients after controlling for more demographic, medical and psychological characteristics, and whether the timing of AF onset in relation to HF diagnosis independently contributed to cognitive function in HF patients with AF. A total of 188 hospitalized HF patients (62.8% male, age 66.3±10.6 years) completed cognitive function assessment with the Montreal Cognitive Assessment (MoCA). A history of AF, along with other medical characteristics, was ascertained through a review of participants' medical charts. The timing of AF onset in relation to HF diagnosis was categorized into AF occurring prior to HF diagnosis (i.e. prior AF) and AF developing after HF diagnosis (i.e. incident AF). Altogether 72 participants had a positive diagnostic history of AF. Specifically, 41 had prior AF, and 31 developed AF subsequently. In HF patients, AF was associated with poorer performance on cognitive function after controlling for more confounders (β=-0.112, ΔR 2 =0.010, p=0.046). Among HF patients with AF, incident AF independently predicted poorer cognitive function (β=-0.238, ΔR 2 =0.027, p=0.047). AF independently contributes to cognitive function in HF patients after adjusting for more confounding variables. The timing of AF onset in relation to HF diagnosis independently predicts cognitive function in HF patients with AF. Prospective studies are needed to elucidate possible mechanisms for the association between AF and cognitive function in HF populations.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.

PubMed

Kaitani, Kazuaki; Inoue, Koichi; Kobori, Atsushi; Nakazawa, Yuko; Ozawa, Tomoya; Kurotobi, Toshiya; Morishima, Itsuro; Miura, Fumiharu; Watanabe, Tetsuya; Masuda, Masaharu; Naito, Masaki; Fujimoto, Hajime; Nishida, Taku; Furukawa, Yoshio; Shirayama, Takeshi; Tanaka, Mariko; Okajima, Katsunori; Yao, Takenori; Egami, Yasuyuki; Satomi, Kazuhiro; Noda, Takashi; Miyamoto, Koji; Haruna, Tetsuya; Kawaji, Tetsuma; Yoshizawa, Takashi; Toyota, Toshiaki; Yahata, Mitsuhiko; Nakai, Kentaro; Sugiyama, Hiroaki; Higashi, Yukei; Ito, Makoto; Horie, Minoru; Kusano, Kengo F; Shimizu, Wataru; Kamakura, Shiro; Morimoto, Takeshi; Kimura, Takeshi; Shizuta, Satoshi

2016-02-14

Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation

PubMed Central

Gasparini, Maurizio; Auricchio, Angelo; Metra, Marco; Regoli, François; Fantoni, Cecilia; Lamp, Barbara; Curnis, Antonio; Vogt, Juergen; Klersy, Catherine

2008-01-01

Aims To investigate the effects of cardiac resynchronization therapy (CRT) on survival in heart failure (HF) patients with permanent atrial fibrillation (AF) and the role of atrio-ventricular junction (AVJ) ablation in these patients. Methods and results Data from 1285 consecutive patients implanted with CRT devices are presented: 1042 patients were in sinus rhythm (SR) and 243 (19%) in AF. Rate control in AF was achieved by either ablating the AVJ in 118 patients (AVJ-abl) or prescribing negative chronotropic drugs (AF-Drugs). Compared with SR, patients with AF were significantly older, more likely to be non-ischaemic, with higher ejection fraction, shorter QRS duration, and less often received ICD back-up. During a median follow-up of 34 months, 170/1042 patients in SR and 39/243 in AF died (mortality: 8.4 and 8.9 per 100 person-year, respectively). Adjusted hazard ratios were similar for all-cause and cardiac mortality [0.9 (0.57–1.42), P = 0.64 and 1.00 (0.60–1.66) P = 0.99, respectively]. Among AF patients, only 11/118 AVJ-abl patients died vs. 28/125 AF-Drugs patients (mortality: 4.3 and 15.2 per 100 person-year, respectively, P < 0.001). Adjusted hazard ratios of AVJ-abl vs. AF-Drugs was 0.26 [95% confidence interval (CI) 0.09–0.73, P = 0.010] for all-cause mortality, 0.31 (95% CI 0.10–0.99, P = 0.048) for cardiac mortality, and 0.15 (95% CI 0.03–0.70, P = 0.016) for HF mortality. Conclusion Patients with HF and AF treated with CRT have similar mortality compared with patients in SR. In AF, AVJ ablation in addition to CRT significantly improves overall survival compared with CRT alone, primarily by reducing HF death. PMID:18390869

Histopathologic analysis of atrial tissue in patients with atrial fibrillation: comparison between patients with atrial septal defect and patients with mitral valvular heart disease.

PubMed

Kwak, Jae Gun; Seo, Jeong-Wook; Oh, Sam Se; Lee, Sang Yun; Ham, Eui Keun; Kim, Woong-Han; Kim, Soo-Jin; Bae, Eun Jung; Lim, Cheoung; Lee, Chang-Ha; Lee, Cheul

2014-01-01

Atrial fibrillation (AF) in adult patients with atrial septal defect (ASD) accompanies an enlarged right atrium (RA) with a less enlarged left atrium (LA), which is the opposite situation in patients with AF and mitral valvular disease. This study was to compare the histopathological change in the atrium of patients with AF of two different etiologies: ASD and mitral disease. Twenty-four patients were enrolled. Group 1 included patients with ASD (8), Group 2 included patients with ASD with AF (6), and Group 3 included patients with mitral disease with AF (10). Preoperative atrial volumes were measured. Atrial tissues were obtained during surgical procedures and stained with periodic acid-Schiff, smooth muscle actin, Sirius red, and Masson's trichrome to detect histopathologic changes compatible with AF. The severity of histopathological changes was represented with "positivity" and "strong positivity" after analyzing digitalized images of the staining. We investigated the relationship between the degree of atrial dilatation and severity of histopathological changes according to the groups and tissues. Group 2 and Group 3 patients showed a tendency toward an enlarged RA volume and enlarged LA volume, respectively, compared with each others. However, in the histopathologic analysis, "positivity" and "strong positivity" showed no significant positive correlations with the degree of atrial volume in special staining. A similar degree of histopathologic changes was observed in both atria in patients with AF (Group 2 and 3) regardless of the degree of dilatation of atrial volume and disease entities. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Aspergillus sensitization or carriage in cystic fibrosis patients.

PubMed

Fillaux, Judith; Brémont, François; Murris, Marlène; Cassaing, Sophie; Tétu, Laurent; Segonds, Christine; Pipy, Bernard; Magnaval, Jean-François

2014-07-01

Aspergillus fumigatus (Af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. This work aimed to identify possible predictive factors for patients who become sensitized to Af, compared with a control group of non-sensitized Af carriers. Between 1995 and 2007, 117 pediatric patients were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1 were recorded. The presence of Af in sputum, the levels of Af-precipitin, total IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were divided into 2 groups: (1) "sensitization": level of Af-IgE > 0.35 IU/mL with t-IgE level < 500 IU/mL and (2) "persistent or transient carriage": Af-IgE level ≤ 0.35 IU/mL with either an Af transient or persistent positive culture. A survival analysis was performed with the appearance of Af-IgE in serum as an outcome variable. Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70% of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and 1.9, respectively) were predictive factors for sensitization. We propose a timeline of the biological events and a tree diagram for risk calculation. Two profiles of cystic fibrosis patients can be envisaged: (1) patients with nonsevere mutation but low FEV1 baselines are becoming colonized with Af or (2) patients with high FEV1 baselines who present with severe mutation are more susceptible to the Af sensitization and then to the presentation of an allergic bronchopulmonary aspergillosis event.

HPLC-HG-AFS determination of arsenic species in acute promyelocytic leukemia (APL) plasma and blood cells.

PubMed

Guo, Meihua; Wang, Wenjing; Hai, Xin; Zhou, Jin

2017-10-25

Arsenic trioxide (ATO) has been successfully used in the treatment of acute promyelocytic leukemia (APL). To clarify the arsenic species in APL patients, high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) and HG-AFS methods were developed and validated to quantify the plasma concentrations of inorganic arsenic (As(III) and As(V)) and methylated metabolites (MMA and DMA), and the total amounts of arsenic in blood cells and plasma. Blood cells and plasma were digested with mixtures of HNO 3 H 2 O 2 and analyzed by HG-AFS. For arsenic speciation, plasma samples were prepared with perchloric acid to precipitate protein. The supernatant was separated on an anion-exchange column within 6min with isocratic elution using 13mM CH 3 COONa, 3mM NaH 2 PO 4 , 4mM KNO 3 and 0.2mM EDTA-2Na. The methods provided linearity range of 0.2-20ng/mL for total arsenic and 2.0-50ng/mL for four arsenic species. The developed methods for total arsenic and arsenic species determination were precise and accurate. The spiked recoveries ranged from 81.2%-108.6% and the coefficients of variation for intra- and inter-batch precision were less than 9.3% and 12.5%, respectively. The developed methods were applied successfully for the assay of total arsenic and arsenic species in 5 APL patients. The HPLC-HG-AFS may be a good alternative for arsenic species determination in APL patients with its simplicity and low-cost in comparison with HPLC-ICP-MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

PubMed

Konno, K; Hisada, M; Naoki, H; Itagaki, Y; Kawai, N; Miwa, A; Yasuhara, T; Morimoto, Y; Nakata, Y

2000-11-01

A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

The modified stepwise ablation guided by low-dose ibutilide in chronic atrial fibrillation trial (The MAGIC-AF Study).

PubMed

Singh, Sheldon M; d'Avila, Andre; Kim, Young-Hoon; Aryana, Arash; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Barrett, Conor D; Heist, E Kevin; Parides, Michael K; Thorpe, Kevin E; Reddy, Vivek Y

2016-05-21

Complex fractionated atrial electrograms (CFAE) are targeted during persistent atrial fibrillation (AF) ablation. However, many CFAE sites are non-specific resulting in extensive ablation. Ibutilide has been shown to reduce left atrial surface area exhibiting CFAE. We hypothesized that ibutilide administration prior to CFAE ablation would identify sites critical for persistent AF maintenance allowing for improved procedural efficacy and long-term freedom from atrial arrhythmias. Two hundred patients undergoing a first-ever persistent AF catheter ablation procedure were randomly assigned to receive either 0.25 mg of intravenous ibutilide or saline placebo upon completion of pulmonary vein isolation. Complex fractionated atrial electrogram sites were then targeted with ablation. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Similar procedural characteristics (procedure, fluoroscopy, and ablation times) were observed with both strategies despite a greater reduction in left atrial surface area with CFAE sites (8 vs. 1%, P < 0.0001) and AF termination during CFAE ablation with ibutilide compared with placebo (75 vs. 57%, P = 0.007). The primary efficacy endpoint was achieved in 56% of patients receiving ibutilide and 49% receiving placebo (P = 0.35). No significant differences in peri-procedural complications were observed in both groups. Despite a reduction in CFAE area and greater AF termination during CFAE ablation, procedural characteristics and clinical outcomes were unchanged when CFAE ablation was guided by ibutilide administration. ClinicalTrials.gov number: NCT01014741. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study.

PubMed

de Andrés-Nogales, F; Oyagüez, I; Betegón-Nicolás, L; Canal-Fontcuberta, C; Soto-Álvarez, J

2015-03-01

Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Tatalina AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1983-03-01

M’CROCOpy pESLUTONEST CkA~l PH THIS SHEET Af) m r’",I "er-"i cprit, r I ~~~~Tahen 01.-ing ,lt c’, ’ .c,- us. Bel ii % owe i -r LEVEL ~ut with Ier r iNVENTORY...82172 MAR N 62 53 W V558 ELV: 964 FT PAT. PAinTS A-F HOURS SU M &UZED: OOOOZ - 230OZ PER{IOD OF RECORD: HOUPLY OBSERYATION.1: JAN 73 - DEC 81 SLW4MAY OF...NOVEM_ _ _ _ .._ ,- .- ,z. 702315 SA A. i. ts 58 9 STATION LOCATION AND INS’rRUMtNTATION ,HI STORY NUr! TIf E 11T to tw ITLmU am M GS of CEO(IAPNICAL

Sparrevohn AFS, Alaska. Revised Uniform Summary of Surface Weather Observations.

DTIC Science & Technology

1985-09-18

SSURFACE WEATHER OBSERVATIONS SPARREVOHN AFS AK MSC #702350 N 61 06 W155 35 ELEV: 1573 FT PASV PARTS A-F HOURS SUMMARIZED: 0000 - 2300 LST PERIOD OF RECORD...stations around the world. This is the provenance of the number (e.g., MSC 999999) which will appear on future OL-A standard products. D I...AFS Af PEt 7oif of [ COPD : 77-84 MONTH: A W, HO URS4LS3: ALL 7.3 itIts 816181L1F7 IN 6FAFLIF WILCS INs ((I (F IF F G CF b t I, [ CF ŕ 6 1 ,F F F tF7F I

The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

DTIC Science & Technology

2015-10-01

mutation, U2AF1(S34F), on hematopoiesis and pre-mRNA splicing in vivo, we created doxycycline-inducible U2AF1(WT) and U2AF1(S34F) transgenic mice...U2AF1(S34F) versus U2AF1(WT). Together, these results suggest that mutant U2AF1 expression contributes to the altered hematopoiesis and pre-mRNA...Spliceosome, Mouse Model, Hematopoiesis , RNA-seq, U2AF1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME

Vitamin K antagonist control in patients with atrial fibrillation in Asia compared with other regions of the world: Real-world data from the GARFIELD-AF registry.

PubMed

Oh, Seil; Goto, Shinya; Accetta, Gabriele; Angchaisuksiri, Pantep; Camm, A John; Cools, Frank; Haas, Sylvia; Kayani, Gloria; Koretsune, Yukihiro; Lim, Toon Wei; Misselwitz, Frank; van Eickels, Martin; Kakkar, Ajay K

2016-11-15

To compare the distribution of international normalized ratios (INRs) in patients receiving vitamin K antagonist (VKA) for newly diagnosed atrial fibrillation in Eastern and Southeastern Asia and in other regions of the world (ORW) represented in the ongoing, global observational study GARFIELD-AF. 3621 and 13,541 patients were recruited prospectively in 2010-2013 from Asia and ORW, respectively. At baseline, excluding patients with unknown antithrombotic treatment, 1356 (37.8%) in Asia and 7081 (53.3%) in ORW received VKA (±antiplatelets). INR readings during 1-year follow-up were analyzed for VKA-treated patients with ≥3 measurements (878 [64.7%] patients in Asia, 4452 [62.9%] in ORW). VKA-treated patients in Asia were younger than those in ORW (mean 67.1 vs 71.3years), with a lower CHA 2 DS 2 -VASc score (3.0 vs 3.5), but a similar HAS-BLED score (1.3 vs 1.4). Mean INR was lower in Asia than in ORW (2.0 vs 2.4). The proportion of time in the therapeutic range, defined using the multinational target of 2.0-3.0, was substantially lower in Asia (31.1% vs 54.1%). In Asia and ORW, 59.3% and 28.2% of INRs were <2, and 9.6% and 17.7% were >3, respectively. The same trend was found in different age groups (<65, 65-74, ≥75years). GARFIELD-AF data demonstrate a difference in the distribution of INRs in patients from Asia versus other regions under current real-world practice. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Use of Oral Steroid and its Effects on Atrial Fibrillation Recurrence and Inflammatory Cytokines Post Ablation - The Steroid AF Study.

PubMed

Iskandar, Sandia; Reddy, Madhu; Afzal, Muhammad R; Rajasingh, Johnson; Atoui, Moustapha; Lavu, Madhav; Atkins, Donita; Bommana, Sudha; Umbarger, Linda; Jaeger, Misty; Pimentel, Rhea; Dendi, Raghuveer; Emert, Martin; Turagam, Mohit; Di Biase, Luigi; Natale, Andrea; Lakkireddy, Dhanunjaya

2017-01-01

Use of corticosteroids before and after atrial fibrillation (AF) ablation can decrease acute inflammation and reduce AF recurrence. To assess the efficacy of oral prednisone in improving the outcomes of pulmonary vein isolation with radiofrequency ablation and its effect on inflammatory cytokine. A total of 60 patients with paroxysmal AF undergoing radiofrequency ablation were randomized (1:1) to receive either 3 doses of 60 mg daily of oral prednisone or a placebo. Inflammatory cytokine levels (TNF-α, IL-1, IL6, IL-8) were measured at baseline, prior to ablation, immediately after ablation, and 24 hours post ablation. Patients underwent 30 day event monitoring at 3 months, 6 months and 12 months post procedure. Immediate post ablation levels of inflammatory cytokines were lower in the steroid group when compared to the placebo group; IL-6: 9.0 ±7 vs 15.8 ±13 p=0.031; IL-8: 10.5 ±9 vs 15.3 ±8; p=0.047 respectively. Acute PV reconnection rates during the procedure (7/23% vs 10/36%; p = 0.39), and RF ablation time (51±13 vs 56±11 min, p = 0.11) trended to be lower in the placebo group than the steroid group. There was no difference in the incidence of early recurrence of AF during the blanking period and freedom from AF off AAD at 12 months between both groups (5/17% vs 8/27%; p = 0.347 and 21/70% vs 18/60%; p=0.417 in placebo and steroid groups respectively). Although oral corticosteroids have significant effect in lowering certain cytokines, it did not impact the clinical outcomes of AF ablation.

Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice.

PubMed

Caudell, David; Harper, David P; Novak, Rachel L; Pierce, Rachel M; Slape, Christopher; Wolff, Linda; Aplan, Peter D

2010-02-11

The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.

Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice

PubMed Central

Caudell, David; Harper, David P.; Novak, Rachel L.; Pierce, Rachel M.; Slape, Christopher; Wolff, Linda

2010-01-01

The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10. PMID:20007546

Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

PubMed

Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

2016-04-01

Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adiabatic Compression Sensitivity of AF-M315E (Briefing Charts)

DTIC Science & Technology

2015-07-27

Charts 3. DATES COVERED (From - To) July 2015-July 2015 4. TITLE AND SUBTITLE Adiabatic Compression Sensitivity of AF - M315E (Briefing Charts) 5a...PA#15402. 14. ABSTRACT The Air Force Research Laboratory developed monopropellant, AF - M315E , has been selected for demonstration under the NASA...Pollux Drive, Edwards AFB, CA 93524-7048. Adiabatic Compression Sensitivity of AF - M315E Phu Quach ERC, Incorporated Air Force Research Laboratory

Atrial Fibrillation Patients Treated With Long-Term Warfarin Anticoagulation Have Higher Rates of All Dementia Types Compared With Patients Receiving Long-Term Warfarin for Other Indications.

PubMed

Bunch, T Jared; May, Heidi T; Bair, Tami L; Crandall, Brian G; Cutler, Michael J; Day, John D; Jacobs, Victoria; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C

2016-07-11

The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long-term anticoagulation exposure. A total of 10 537 patients anticoagulated with warfarin (target INR 2-3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF. The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001). A propensity analysis of 6030 patients was performed to account for baseline demographics differences. Long-term risk of dementia remained significant in AF patients compared with matched non-AF patients (total dementia: hazard ratio [HR]=2.42 [1.85-3.18], P<0.0001; Alzheimer: HR=2.04 [1.40-2.98], P<0.0001; senile: HR=2.46 [1.58-3.86], P<0.0001). Low percent therapeutic range compared with a higher percent therapeutic range was associated with dementia risk in both AF (26-50% versus >75%: HR=2.51, P=0.005) and non-AF groups (≤25% versus >75%: HR=3.92, P<0.0001). The presence of AF significantly increases risk of dementia, including Alzheimer's disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients. © 2016 The Authors. Published on behalf of the American Heart

Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European Registry in Atrial Fibrillation (PREFER in AF).

PubMed

Kirchhof, Paulus; Ammentorp, Bettina; Darius, Harald; De Caterina, Raffaele; Le Heuzey, Jean-Yves; Schilling, Richard John; Schmitt, Josef; Zamorano, Jose Luis

2014-01-01

We sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology. The PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard deviation). Thirty per cent patients had paroxysmal, 24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent AF. Oral anticoagulation was used in the majority of patients: 4799 patients (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate 60-100 bpm). Half of the patients (50.7%) received rhythm control therapy by electrical cardioversion (18.1%), pharmacological cardioversion (19.5%), antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol 5.5%, dronedarone 4.0%), and catheter ablation (5.0%). The management of AF patients in 2012 has adapted to recent evidence and guideline recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given to over 80% of eligible patients, including those at risk for bleeding. Rate is often adequately controlled, and rhythm control therapy is widely used.

AF RPA Training: Utility and Tradition in Conflict

DTIC Science & Technology

2017-06-01

The AF and the Army offer competing views on the future of UAS training . Both services export its cultural values, as the Navy, USMC, and...and visions. Despite common technologies, each service approached UAS from different starting points, and created different training models. The AF...issues reflected different approaches each service took to Unmanned Aerial Systems (UAS) operational employment, personnel management, and training

Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

PubMed

Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

2014-06-01

Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

A Prospective Survey of Atrial Fibrillation Management for Real-world Guideline Adherence: COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) Registry.

PubMed

Kim, Hyeongsoo; Kim, Tae Hoon; Cha, Myung Jin; Lee, Jung Myung; Park, Junbeom; Park, Jin Kyu; Kang, Ki Woon; Shim, Jaemin; Uhm, Jae Sun; Kim, Jun; Park, Hyung Wook; Choi, Eue Keun; Kim, Jin Bae; Kim, Changsoo; Lee, Young Soo; Joung, Boyoung

2017-11-01

The aging population is rapidly increasing, and atrial fibrillation (AF) is becoming a significant public health burden in Asia, including Korea. This study evaluated current treatment patterns and guideline adherence of AF treatment. In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were consecutively enrolled between June 2016 and April 2017 from 10 tertiary hospitals in Korea. The AF type was paroxysmal, persistent, and permanent in 65.3%, 30.0%, and 2.9% of patients, respectively. Underlying structural heart disease was present in 11.9%. Mean CHA₂DS₂-VASc was 2.7±1.7. Oral anticoagulation (OAC), rate control, and rhythm control were used in 70.1%, 53.9%, and 54.4% of patients, respectively. OAC was performed in 82.7% of patients with a high stroke risk. However, antithrombotic therapy was inadequately used in 53.4% of patients with a low stroke risk. For rate control in 192 patients with low ejection fraction (<40%), β-blocker (65.6%), digoxin (5.2%), or both (19.3%) were adequately used in 90.1% of patients; however, a calcium channel blocker was inadequately used in 9.9%. A rhythm control strategy was chosen in 54.4% of patients. The prescribing rate of class Ic antiarrythmics, dronedarone, and sotalol was 16.9% of patients with low ejection fraction. This study shows how successfully guidelines can be applied in the real world. The nonadherence rate was 17.2%, 9.9%, and 22.4% for stroke prevention, rate control, and rhythm control, respectively. Copyright © 2017. The Korean Society of Cardiology

Dental Laboratory Career Ladder AFS 982X0.

DTIC Science & Technology

1982-09-01

7ADA120 102 AIR FORCE OCCUPATIONAL MEASUREMENT CENTER RANDOLPH AFB TX F/6 Ri9 DENTAL LABORATORY CAREER LADDER AFS 982XO.(U) UNCLASSIFIED NLEEEili E...Eli E~lllllllllEEE EEEEEIIIEEEEEE EIEEEEIIEEEEEE IIIIIIIIIIIIIIlLZ UNITED STATES AIR FORCE 0! DENTAL LABORATORY CAREER LADDER DTlC AFS 982X0 ELEr.L_...LADDER STRUCTURE GROUPS ----------------------------------- 57 APPENDIX B - JOB DESCRIPTIONS FOR BASE AND AREA DENTAL LABORATORY PERSONNEL

Rates of Atrial Fibrillation in Black Versus White Patients With Pacemakers.

PubMed

Kamel, Hooman; Kleindorfer, Dawn O; Bhave, Prashant D; Cushman, Mary; Levitan, Emily B; Howard, George; Soliman, Elsayed Z

2016-02-12

Black US residents experience higher rates of ischemic stroke than white residents but have lower rates of clinically apparent atrial fibrillation (AF), a strong risk factor for stroke. It is unclear whether black persons truly have less AF or simply more undiagnosed AF. We obtained administrative claims data from state health agencies regarding all emergency department visits and hospitalizations in California, Florida, and New York. We identified a cohort of patients with pacemakers, the regular interrogation of which reduces the likelihood of undiagnosed AF. We compared rates of documented AF or atrial flutter at follow-up visits using Kaplan-Meier survival statistics and Cox proportional hazards models adjusted for demographic characteristics and vascular risk factors. We identified 10 393 black and 91 380 white patients without documented AF or atrial flutter before or at the index visit for pacemaker implantation. During 3.7 (±1.8) years of follow-up, black patients had a significantly lower rate of AF (21.4%; 95% CI 19.8-23.2) than white patients (25.5%; 95% CI 24.9-26.0). After adjustment for demographic characteristics and comorbidities, black patients had a lower hazard of AF (hazard ratio 0.91; 95% CI 0.86-0.96), a higher hazard of atrial flutter (hazard ratio 1.29; 95% CI 1.11-1.49), and a lower hazard of the composite of AF or atrial flutter (hazard ratio 0.94; 95% CI 0.88-99). In a population-based sample of patients with pacemakers, black patients had a lower rate of AF compared with white patients. These findings indicate that the persistent racial disparities in rates of ischemic stroke are likely to be related to factors other than undiagnosed AF. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need for...

Cost-Effectiveness of Percutaneous Closure of the Left Atrial Appendage in Atrial Fibrillation Based on Results From PROTECT AF Versus PREVAIL.

PubMed

Freeman, James V; Hutton, David W; Barnes, Geoffrey D; Zhu, Ruo P; Owens, Douglas K; Garber, Alan M; Go, Alan S; Hlatky, Mark A; Heidenreich, Paul A; Wang, Paul J; Al-Ahmad, Amin; Turakhia, Mintu P

2016-06-01

Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost effectiveness compared with anticoagulation has not been evaluated using all available contemporary trial data. We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation (PROTECT AF) and Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation (PREVAIL) randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios compared with warfarin and dabigatran were $20 486 and $23 422 per quality-adjusted life year, respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 quality-adjusted life years, respectively) and more costly. At a willingness-to-pay threshold of $50 000 per quality-adjusted life year, LAA closure was cost effective 90% and 9% of the time under PROTECT AF and PREVAIL assumptions, respectively. These results were sensitive to the rates of ischemic stroke and intracranial hemorrhage for LAA closure and medical anticoagulation. Using data from the PROTECT AF trial, LAA closure with the Watchman device was cost effective; using PREVAIL trial data, Watchman was more costly and less effective than warfarin and dabigatran. PROTECT AF enrolled more patients and has substantially longer follow-up time, allowing greater statistical certainty with the cost-effectiveness results. However, longer-term trial results and postmarketing surveillance of major adverse events will be vital to determining the value of the Watchman in clinical

[Galectin-3 in Patients With Paroxysmal and Persistent Atrial Fibrillation and Metabolic Syndrome].

PubMed

A, V A; Zaslavskaya, E L; Soboleva, A V; Baranova, E I; Listopad, O V; Nifontov, S E; Nrady, A O; Shlyakhto, E V

2016-06-01

To evaluate serum galectin 3 and to determine the potential clinical value of this parameter in patients with atrial fibrillation - AF (paroxysmal and persistent) and metabolic syndrome (MS). We examined 100 patients with MS (50 with paroxysmal or persistent AF and 50 without arrhythmia) and 50 healthy persons. Serum galectin 3 measured by ELISA method, ECHO cardiography was performed to all examined persons. Galectin 3 in patients with MS and AF was higher, than in patients with MS without arrhythmia and much more higher than galectin 3 in healthy persons 0,72 (0,44;1,36), 0,44 (0,42;1,22) and 0,32 (0,28;0,42) ng/ml (<0,01). In patients with persistent AF levels of galectin 3 is higher than in patients with paroxysmal AF. Positive correlation between the levels of galectin 3 and duration arrhythmia was revealed (r=0,301; p<0,01). Higher level of galectin 3 was revealed in patients with frequent paroxysms of AF and ineffective antiarrhythmic therapy. Marker of myocardial fibrosis serum galectin 3 in patients with atrial fibrillation and metabolic syndrome is higher than in patients with the metabolic syndrome, without this arrhythmia and higher than in healthy controls. In patients with persistent AF level of galectin 3 was higher than in patients with paroxysmal AF.

Standardized Prevalence Ratios for Atrial Fibrillation in Adult Dialysis Patients in Japan.

PubMed

Ohsawa, Masaki; Tanno, Kozo; Okamura, Tomonori; Yonekura, Yuki; Kato, Karen; Fujishima, Yosuke; Obara, Wataru; Abe, Takaya; Itai, Kazuyoshi; Ogasawara, Kuniaki; Omama, Shinichi; Turin, Tanvir Chowdhury; Miyamatsu, Naomi; Ishibashi, Yasuhiro; Morino, Yoshihiro; Itoh, Tomonori; Onoda, Toshiyuki; Kuribayashi, Toru; Makita, Shinji; Yoshida, Yuki; Nakamura, Motoyuki; Tanaka, Fumitaka; Ohta, Mutsuko; Sakata, Kiyomi; Okayama, Akira

2016-05-05

While it is assumed that dialysis patients in Japan have a higher prevalence of atrial fibrillation (AF) than the general population, the magnitude of this difference is not known. Standardized prevalence ratios (SPRs) for AF in dialysis patients (n = 1510) were calculated compared to data from the general population (n = 26 454) living in the same area. The prevalences of AF were 3.8% and 1.6% in dialysis patients and the general population, respectively. In male subjects, these respective values were 4.9% and 3.3%, and in female subjects they were 1.6% and 0.6%. The SPRs for AF were 2.53 (95% confidence interval [CI], 1.88-3.19) in all dialysis patients, 1.80 (95% CI, 1.30-2.29) in male dialysis patients, and 2.13 (95% CI, 0.66-3.61) in female dialysis patients. The prevalence of AF in dialysis patients was twice that in the population-based controls. Since AF strongly contributes to a higher risk of cardiovascular mortality and morbidity in the general population, further longitudinal studies should be conducted regarding the risk of several outcomes attributable to AF among Japanese dialysis patients.

Atrial fibrillation patients with isolated pulmonary veins: Is sinus rhythm achievable?

PubMed

Szilágyi, Judit; Marcus, Gregory M; Badhwar, Nitish; Lee, Byron K; Lee, Randall J; Vedantham, Vasanth; Tseng, Zian H; Walters, Tomos; Scheinman, Melvin; Olgin, Jeffrey; Gerstenfeld, Edward P

2017-07-01

The cornerstone of atrial fibrillation (AF) ablation is isolation of the pulmonary veins (PVs). Patients with recurrent AF undergoing repeat ablation usually have PV reconnection (PVr). The ablation strategy and outcome of patients undergoing repeat ablation who have persistent isolation of all PVs (PVi) at the time of repeat ablation is unknown. We studied consecutive patients with recurrent AF undergoing repeat ablation and compared patients with PVi to those with PVr. One hundred fifty-two patients underwent repeat ablation, and of these, 25 patients (16.4%) had PVi. Patients with PVi underwent ablation targeting any isoproterenol induced AF triggers, atrial substrate, or inducible atrial tachycardias or flutters. Patients with PVi compared to PVr were more likely to have a history of persistent AF (64% vs. 26%; P < 0.0001), obesity (BMI 30.4 vs. 28.2; P = 0.05), and prior use of contact force sensing catheters (28% vs. 0.8%, P < 0.0001). After a mean follow-up of 19 ± 15 months, 56% of PVi patients remained in sinus rhythm compared to 76.3% of PVr patients (P = 0.036). In a multivariable model, PVi patients and those with cardiomyopathy had a higher risk of recurrent atrial tachyarrhythmias (HR = 3.6 95%, CI 1.6-8.3, P = 0.002 and HR = 6.2, 95% CI 2.3-16.3, P < 0.0001, respectively). In patients who have all PVs isolated at the time of the redo AF ablation, a strategy of targeting non-PV AF triggers and inducible flutters can still lead to AF freedom in more than half of patients. Patients with PVr, however, have a better long-term outcome. © 2017 Wiley Periodicals, Inc.

Extracting uranium from seawater: Promising AF series adsorbents

DOE PAGES

Das, Sadananda; Oyola, Y.; Mayes, Richard T.; ...

2015-11-02

Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8more » ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.« less

Extracting Uranium from Seawater: Promising AF Series Adsorbents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, S.; Oyola, Y.; Mayes, Richard T.

A new family of high-surface-area polyethylene fiber adsorbents named the AF series was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series adsorbents were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/comonomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154-354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44 M KOH at 80 °C followed by screening at ORNL with sodium-based synthetic aqueous solution, spiked withmore » 8 ppm uranium. The uranium adsorption capacity in simulated seawater screening ranged from 170 to 200 g-U/kg-ads irrespective of %DOG. A monomer/comonomer molar ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through column experiments to determine uranium loading capacity with varying KOH conditioning times at 80 °C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1 and 3 h of KOH conditioning at 80 °C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 1 to 3 h at 80 °C resulted in a 22-27% decrease in uranium adsorption capacity in seawater.« less

Extracting uranium from seawater: Promising AF series adsorbents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Sadananda; Oyola, Y.; Mayes, Richard T.

Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8more » ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.« less

Automated Risk Assessment for Stroke in Atrial Fibrillation (AURAS-AF)--an automated software system to promote anticoagulation and reduce stroke risk: study protocol for a cluster randomised controlled trial.

PubMed

Holt, Tim A; Fitzmaurice, David A; Marshall, Tom; Fay, Matthew; Qureshi, Nadeem; Dalton, Andrew R H; Hobbs, F D Richard; Lasserson, Daniel S; Kearley, Karen; Hislop, Jenny; Jin, Jing

2013-11-13

Patients with atrial fibrillation (AF) are at significantly increased risk of stroke. Oral anticoagulants (OACs) substantially reduce this risk, with gains seen across the spectrum of baseline risk. Despite the benefit to patients, OAC prescribing remains suboptimal in the United Kingdom (UK). We will investigate whether an automated software system, operating within primary care electronic medical records, can improve the management of AF by identifying patients eligible for OAC therapy and increasing uptake of this treatment. We will conduct a cluster randomised controlled trial, involving general practices using the Egton Medical Information Systems (EMIS) Web clinical system. We will randomise practices to use an electronic software tool or to continue with usual care. The tool will a) produce (and continually refresh) a list of patients with AF who are eligible for OAC therapy--practices will invite these patients to discuss therapy at the start of the trial--and b) generate electronic screen reminders in the medical records of those eligible, appearing throughout the trial. The software will run for 6 months in 23 intervention practices. A total of 23 control practices will manage their AF register in line with the usual care offered. The primary outcome is change in proportion of eligible patients with AF who have been prescribed OAC therapy after six months. Secondary outcomes are incidence of stroke, transient ischaemic attack, other major thromboembolism, major haemorrhage and reports of inappropriate OAC prescribing in the data collection sample--those deemed eligible for OACs. We will conduct a process evaluation in parallel with the randomised trial. We will use qualitative methods to examine patient and practitioner views of the intervention and its impact on primary care practice, including its time implications. AURAS-AF will investigate whether a simple intervention, using electronic primary care records, can improve OAC uptake in a high risk group

Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation: Insights from the ARISTOTLE trial.

PubMed

Guimarães, Patrícia O; Wojdyla, Daniel M; Alexander, John H; Thomas, Laine; Alings, Marco; Flaker, Greg C; Al-Khatib, Sana M; Hanna, Michael; Horowitz, John D; Wallentin, Lars; Granger, Christopher B; Lopes, Renato D

2017-01-15

Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed AF had a similar risk of stroke/systemic embolism (HR=1.07, 95% CI=0.80-1.42; p=0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR=1.21, 95% CI=1.02-1.43; p=0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AF diagnosis (all interaction p-values >0.12). Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Proteins and antibodies in serum, plasma, and whole blood-size characterization using asymmetrical flow field-flow fractionation (AF4).

PubMed

Leeman, Mats; Choi, Jaeyeong; Hansson, Sebastian; Storm, Matilda Ulmius; Nilsson, Lars

2018-05-29

The analysis of aggregates of therapeutic proteins is crucial in order to ensure efficacy and patient safety. Typically, the analysis is performed in the finished formulation to ensure that aggregates are not present. An important question is, however, what happens to therapeutic proteins, with regard to oligomerization and aggregation, after they have been administrated (i.e., in the blood). In this paper, the separation of whole blood, plasma, and serum is shown using asymmetric flow field-flow fractionation (AF4) with a minimum of sample pre-treatment. Furthermore, the analysis and size characterization of a fluorescent antibody in blood plasma using AF4 are demonstrated. The results show the suitability and strength of AF4 for blood analysis and open new important routes for the analysis and characterization of therapeutic proteins in the blood.

CERN’s AFS replacement project

NASA Astrophysics Data System (ADS)

Iven, J.; Lamanna, M.; Pace, A.

2017-10-01

OpenAFS is the legacy solution for a variety of use cases at CERN, most notably home-directory services. OpenAFS has been used as the primary shared file-system for Linux (and other) clients for more than 20 years, but despite an excellent track record, the project’s age and architectural limitations are becoming more evident. We are now working to offer an alternative solution based on existing CERN storage services. The new solution will offer evolved functionality, and is expected to eventually benefit from operational synergies. In this paper we will present CERN’s usage and an analysis of our technical choices: we will focus on the alternatives chosen for the various use cases (among them EOS, CERNBox and CASTOR); on implementing the migration process over the coming years; and the challenges and opportunities of the migration.

Cone Photoreceptor Abnormalities Correlate with Vision Loss in Patients with Stargardt Disease

PubMed Central

Chen, Yingming; Ratnam, Kavitha; Sundquist, Sanna M.; Lujan, Brandon; Ayyagari, Radha; Gudiseva, V. Harini; Roorda, Austin

2011-01-01

Purpose. To study the relationship between macular cone structure, fundus autofluorescence (AF), and visual function in patients with Stargardt disease (STGD). Methods. High-resolution images of the macula were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography in 12 patients with STGD and 27 age-matched healthy subjects. Measures of retinal structure and AF were correlated with visual function, including best-corrected visual acuity, color vision, kinetic and static perimetry, fundus-guided microperimetry, and full-field electroretinography. Mutation analysis of the ABCA4 gene was completed in all patients. Results. Patients were 15 to 55 years old, and visual acuity ranged from 20/25–20/320. Central scotomas were present in all patients, although the fovea was spared in three patients. The earliest cone spacing abnormalities were observed in regions of homogeneous AF, normal visual function, and normal outer retinal structure. Outer retinal structure and AF were most normal near the optic disc. Longitudinal studies showed progressive increases in AF followed by reduced AF associated with losses of visual sensitivity, outer retinal layers, and cones. At least one disease-causing mutation in the ABCA4 gene was identified in 11 of 12 patients studied; 1 of 12 patients showed no disease-causing ABCA4 mutations. Conclusions. AOSLO imaging demonstrated abnormal cone spacing in regions of abnormal fundus AF and reduced visual function. These findings provide support for a model of disease progression in which lipofuscin accumulation results in homogeneously increased AF with cone spacing abnormalities, followed by heterogeneously increased AF with cone loss, then reduced AF with cone and RPE cell death. (ClinicalTrials.gov number, NCT00254605.) PMID:21296825

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

Atrial fibrillation in patients with Wolff-Parkinson-White syndrome: role of pulmonary veins.

PubMed

Derejko, Paweł; Szumowski, Lukasz Jan; Sanders, Prashanthan; Krupa, Wojciech; Bodalski, Robert; Orczykowski, Michał; Urbanek, Piotr; Zakrzewska, Joanna; Lim, Han S; Lau, Dennis H; Kuśnierz, Jacek; Walczak, Franciszek

2012-03-01

We aimed to characterize electrophysiological properties of pulmonary veins (PVs) in patients with Wolff-Parkinson-White (WPW) syndrome and atrial fibrillation (AF), and to compare them to those in patients with WPW without AF. A total of 31 patients (mean age 40 ± 15 years, 23 males) with WPW were recruited: 16 patients with (AF group) and 15 without (controls) a history of AF. The basic electrophysiological (EPS) and echocardiographic data were not different between the 2 groups. Effective refractory periods (ERPs) of PVs were significantly shorter in the AF group compared to controls: left superior (LS) PV ERP 185±29 versus 230 ± 24 ms, P = 0.001; left inferior PV ERP 198 ± 25 versus 219 ± 26 ms, P = 0.04; right superior (RS) PV ERP 207 ± 25 versus 236 ± 19 ms, P = 0.001; right inferior PV ERP 208 ± 30 versus 240 ± 19 ms, P = 0.003. Maximal veno-atrial conduction delay (i.e., the maximal prolongation of interval from stimulus delivered at PV ostia to proximal coronary sinus after extrastimulus compared to the basic drive cycle) was longer in the AF group when pacing from LSPV (69.3 ± 37.9 vs 32.6 ± 16.1 ms, P = 0.01) and RSPV (74.1 ± 25.9 vs 50.2 ± 26.5 ms, P = 0.04). During EPS, AF was induced more often in the AF group (n = 7) compared to controls (n = 1; P = 0.04). Follow-up revealed that AF recurred in 3 patients in the AF group and none of the controls. Patients with WPW syndrome and AF have shorter ERPs of PVs and greater maximal veno-atrial conduction delay compared to patients with WPW without AF. These findings suggest a potential role of PVs in the development of AF in patients with WPW. © 2011 Wiley Periodicals, Inc.

Persistent Atrial Fibrillation Ablation in Females: Insight from the MAGIC-AF Trial.

PubMed

Singh, Sheldon M; D'Avila, Andre; Aryana, Arash; Kim, Young-Hoon; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Heist, E Kevin; Barrett, Conor D; Thorpe, Kevin E; Reddy, Vivek Y

2016-07-27

Atrial fibrillation (AF) ablation is less frequently performed in women when compared to men. There are conflicting data on the safety and efficacy of AF ablation in women. The objective of this study was to compare the clinical characteristics and outcomes in a contemporary cohort of men and women undergoing persistent AF ablation procedures. A total of 182 men and 53 women undergoing a first-ever persistent AF catheter ablation procedure in The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) trial were evaluated. Clinical and procedural characteristics were compared between each gender. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Women undergoing catheter ablation procedures were older than men (P < 0.001). The duration of AF and associated co-morbidities were similar between both genders. Single procedure drug-free atrial arrhythmia recurrence occurred in 53% of the cohort with no difference based on gender (men = 54%, women = 53%; P = 1.0). Procedural (P = 0.04), fluoroscopic (P = 0.02), and ablation times (P = 0.003) were shorter in women compared to men. Periprocedural complications and postablation improvement in quality of life were similar between men and women. Women undergoing a first-ever persistent AF ablation procedure were older but had similar clinical outcomes and complications when compared with men. © 2016 Wiley Periodicals, Inc.

Safety and Efficacy of Rivaroxaban in Patients With Cardiac Implantable Electronic Devices: Observations From the ROCKET AF Trial.

PubMed

Leef, George C; Hellkamp, Anne S; Patel, Manesh R; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Halperin, Jonathan L; Hankey, Graeme J; Hacke, Werner; Nessel, Christopher C; Singer, Daniel E; Fox, Keith A A; Mahaffey, Kenneth W; Piccini, Jonathan P

2017-06-14

Although implantation of cardiac implantable electronic devices (CIEDs) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting. Using data from Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo CIED implantation or revision. In this post-hoc, postrandomization, on-treatment analysis, only the first intervention per patient was analyzed. During a median follow-up of 2.2 years, 453 patients (242 rivaroxaban group; 211 warfarin group) underwent de novo CIED implantation (64.2%) or revision procedures (35.8%). Patients who received CIEDs were older, more likely to be male, and more likely to have past myocardial infarction, but had similar stroke risk compared to patients who did not receive CIEDs. Most patients who received a device had study drug interrupted for the procedure and did not receive bridging anticoagulation. During the 30-day postprocedural period, 11 patients (4.55%) in the rivaroxaban group experienced bleeding complications compared with 15 (7.13%) in the warfarin group. Thromboembolic complications occurred in 3 patients (1.26%) in the rivaroxaban group and 1 (0.48%) in the warfarin group. Event rates were too low for formal hypothesis testing. Bleeding and thromboembolic events were low in both rivaroxaban- and warfarin-treated patients. Periprocedural use of oral factor Xa inhibitors in CIED implantation requires further study in prospective, randomized trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. © 2017 The Authors, Bayer US LLC, and Janssen Research and Development. Published on behalf of the American Heart Association, Inc., by Wiley.

Influence of atrial fibrillation on the mortality of patients with heart failure with preserved ejection fraction.

PubMed

Franco, Jonathan; Formiga, Francesc; Cepeda, Jose; Llacer, Pau; Arévalo-Lorido, Juan; Cerqueiro, Jose; González-Franco, Alvaro; Epelde, Francesc; Manzano, Luis; Montero Pérez-Barquero, Manuel

2018-05-23

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018). In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Embossed Teflon AF Laminate Membrane Microfluidic Diaphragm Valves

NASA Technical Reports Server (NTRS)

Willis, Peter; Hunt, Brian; White,Victor; Grunthaner, Frank

2008-01-01

A microfluidic system has been designed to survive spaceflight and to function autonomously on the Martian surface. It manipulates microscopic quantities of liquid water and performs chemical analyses on these samples to assay for the presence of molecules associated with past or present living processes. This technology lies at the core of the Urey Instrument, which is scheduled for inclusion on the Pasteur Payload of the ESA ExoMars rover mission in 2013. Fabrication processes have been developed to make the microfabricated Teflon-AF microfluidic diaphragm pumps capable of surviving extreme temperature excursions before and after exposure to liquid water. Two glass wafers are etched with features and a continuous Teflon membrane is sandwiched between them (see figure). Single valves are constructed using this geometry. The microfabricated devices are then post processed by heating the assembled device while applying pneumatic pressure to force the Teflon diaphragm against the valve seat while it is softened. After cooling the device, the embossed membrane retains this new shape. This solves previous problems with bubble introduction into the fluid flow where deformations of the membrane at the valve seat occurred during device bonding at elevated temperatures (100-150 C). The use of laminated membranes containing commercial Teflon AF 2400 sheet sandwiched between spun Teflon AF 1600 layers performed best, and were less gas permeable than Teflon AF 1600 membranes on their own. Spinning Teflon AF 1600 solution (6 percent in FLOURINERT(Registered TradeMark) FC40 solvent, 3M Company) at 500 rpm for 1.5 seconds, followed by 1,000 rpm for 3 seconds onto Borofloat glass wafers, results in a 10-micron-thick film of extremely smooth Teflon AF. This spinning process is repeated several times on flat, blank, glass wafers in order to gradually build a thick, smooth membrane. After running this process at least five times, the wafer and Teflon coating are heated under vacuum

Alteration of the SETBP1 gene and splicing pathway genes SF3B1, U2AF1, and SRSF2 in childhood acute myeloid leukemia.

PubMed

Choi, Hyun-Woo; Kim, Hye-Ran; Baek, Hee-Jo; Kook, Hoon; Cho, Duck; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun

2015-01-01

Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.

[Examination of skin autofluorescence for the determination of glycation end-products in patients on chronic hemodialysis].

PubMed

Golubev, R V; Papayan, G V; Glazunova, A A; Korosteleva, N Yu; Petrishchev, N N; Smirnov, A V

2016-01-01

To assess the results of determination of glycation end-products (GEPs) by skin autofluorescence (AF) in patients on chronic hemodialysis (HD). A device made in Russia was used to estimate skin AF intensity in 40 apparently healthy individuals and in 76 patients treated with chronic HD. While analyzing the findings, comparisons were made in both groups; a relationship between skin AF intensity and clinical and laboratory parameters was also investigated in patients on HD. The intensity of AF in the patients treated with chronic HD proved to be significantly higher than that in the control group. There was a direct correlation of the intensity of AF with age in both groups and that with the duration of dialysis treatment in patients on HD. In patients with coronary heart disease, the intensity of AF was significantly higher than in those without this condition. The intensity of AF directly correlated with the Charlson comorbidity index in the patients on HD. There were no correlations of skin AF intensity with main generally detected laboratory blood indicators, body mass index, and the nature of drug therapy in the patients on HD. Tissue GEP levels may serve as a cumulative index of metabolic stress in HD patients. The determination of GEP by measuring the intensity of skin AF may be used to assess prognosis in patients treated with chronic HD.

The AFS Volunteer Resources Study: Summary of Findings from Australia.

ERIC Educational Resources Information Center

Walsh, Desmond; And Others

The American Field Service (AFS) has 3,500 volunteers throughout Australia. Local chapters recruit potential host families and participants. Host families are recruited actively and selectively while volunteers are recruited largely through AFS presentations at schools, through friends, and by returning volunteers. Due to a high level of demand…

Evaluating the HATCH score for predicting progression to sustained atrial fibrillation in ED patients with new atrial fibrillation.

PubMed

Barrett, Tyler W; Self, Wesley H; Wasserman, Brian S; McNaughton, Candace D; Darbar, Dawood

2013-05-01

Atrial fibrillation (AF) is often first detected in the emergency department (ED). Not all AF patients progress to sustained AF (ie, episodes lasting >7 days), which is associated with increased morbidity. The HATCH score stratifies patients with paroxysmal AF according to their risk for progression to sustained AF within 1 year. The HATCH score has previously never been tested in ED patients. We evaluated the accuracy of the HATCH score to predict progression to sustained AF within 1 year of initial AF diagnosis in the ED. We conducted a retrospective cohort study of 253 ED patients with new onset AF and known rhythm status for 1 year following the initial AF detection. The exposure variable was the HATCH score at initial ED evaluation. The primary outcome was rhythm status at 1 year following initial AF diagnosis. We constructed a receiver operating characteristic curve and calculated the area under the curve to estimate the HATCH score's accuracy of predicting progression to sustained AF. Overall, 61 (24%) of 253 of patients progressed to sustained AF within 1 year of initial detection, and the HATCH score receiver operating characteristic area under the curve was 0.62 (95% confidence interval, 0.54-0.70). Among ED patients with new onset AF, the HATCH score was a modest predictor of progression to sustained AF. Because only 2 patients had a HATCH greater than 5, this previously recommended cut-point was not useful in identifying high-risk patients in this cohort. Refinement of this decision aid is needed to improve its prognostic accuracy in the ED population. Copyright © 2013 Elsevier Inc. All rights reserved.

CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation

PubMed Central

Fu, Ailing; Zhu, Huifeng; Ren, Qiao; Wang, Bochu; Xu, Xingran; Bai, Huiyuan; Dong, Cheng

2016-01-01

Melanoma is one of the most lethal forms of skin cancer due to its early metastatic spread. The variant form of CD44 (CD44v), a cell surface glycoprotein, is highly expressed on metastatic melanoma. The mechanisms of regulation of CD44 alternative splicing in melanoma and its pathogenic contributions are so far poorly understood. Here, we investigated the expression level of CD44 in a large set of melanocytic lesions at different stages. We found that the expression of CD44v8-10 and a splicing factor, U2AF2, is significantly increased during melanoma progression, while CD82/KAI1, a tetraspanin family of tumor suppressor, is reduced in metastatic melanoma. CD44v8-10 and U2AF2 expressions which are negatively correlated with CD82 levels are dramatically elevated in primary melanoma compared with dysplastic nevi and further increased in metastatic melanoma. We also showed that patients with higher CD44v8-10 and U2AF2 expression levels tended to have shorter survival. By using both in vivo and in vitro assays, we demonstrated that CD82 inhibits the production of CD44v8-10 on melanoma. Mechanistically, U2AF2 is a downstream target of CD82 and in malignant melanoma facilitates CD44v8-10 alternative splicing. U2AF2-mediated CD44 isoform switch is required for melanoma migration in vitro and lung and liver metastasis in vivo. Notably, overexpression of CD82 suppresses U2AF2 activity by inducing U2AF2 ubiquitination. In addition, our data suggested that enhancement of melanoma migration by U2AF2-dependent CD44v8-10 splicing is mediated by Src/FAK/RhoA activation and formation of stress fibers as well as CD44-E-selectin binding reinforcement. These findings uncovered a hitherto unappreciated function of CD82 in severing the linkage between U2AF2-mediated CD44 alternative splicing and cancer aggressiveness, with potential prognostic and therapeutic implications in melanoma. PMID:27041584

[Characteristics and outcome of acute ischemic stroke patients with atrial fibrillation].

PubMed

Li, Shenjun; Wang, Shucai; Gu, Mingming; Cao, Bingzhen

2015-11-17

To evaluate clinical characteristics and outcome of acute ischemic stroke patients with atrial fibrillation. Consecutive acute ischemic stroke patients who were hospitalized in the neurology department of General Hospital of Jinan Military Region were prospectively recruited from August 2010 to November 2013.The baseline datum including age, sex, National Institute of Health Stroke Scale (NIHSS), type of Oxfordshire Community Stroke Project (OCSP: total anterior circulation infarct, partial anterior circulation infarction, posterior circulation infarction and lacunar infarction), serum creatinine, serum albumin levels etc.were recorded.Atrial fibrillation (AF) was defined as a history of persistent atrial fibrillation or paroxysmal atrial fibrillation, supported by past electrocardiogram or diagnosed by the attending physicians based on physical examination, electrocardiogram and/or 24-hour electrocardiogram monitoring during hospitalization. Outcome was assessed by modified Rankin Scale (mRS) which was obtained 180 days after stroke by telephone interview (mRS ≤ 2 reflected good prognosis, and mRS>2 reflected unfavorable prognosis), and death defined as all-cause mortality. Multivariate regression model was used to analyze predictors of mortality and disability. Of the 965 patients included in this study, 113 (11.71%) had AF; valvular AF was observed in 11 patients (9.7%) among them.Only 4 patients with valvular AF and none of the patients with non-valvular AF took warfarin before the stroke event. 14.2% (16/113) acute ischemic stroke patients with AF took aspirin. Compared to patients without AF, patients with AF had a higher NIHSS score on admission (median 11 vs 5, P=0.000); were more often with diabetes (26.55% vs 9.74%, P=0.028), congestive heart failure (12.37% vs 11.03%, P=0.000), prior stroke (31.86% vs 21.83%, P=0.023), total anterior circulation infarct subtype (51.33% vs 19.37%, P=0.000); they were less often smokers (20.35% vs 37.32%, P=0

The why, when and how to test for obstructive sleep apnea in patients with atrial fibrillation.

PubMed

Desteghe, Lien; Hendriks, Jeroen M L; McEvoy, R Doug; Chai-Coetzer, Ching Li; Dendale, Paul; Sanders, Prashanthan; Heidbuchel, Hein; Linz, Dominik

2018-04-12

Sleep apnea is associated with increased cardiovascular risk and may be important in atrial fibrillation (AF) management. It is present in up to 62% of the AF population and is highly under-recognized and underdiagnosed. Obstructive sleep apnea (OSA) is strongly associated with AF and non-randomized trials have shown that its treatment can help to reduce AF recurrences and maintain sinus rhythm. The 2016 European Society of Cardiology guidelines for the management of AF recommend that AF patients should be questioned regarding the symptoms of OSA and that OSA-treatment should be optimized to improve AF treatment results. However, strategies on how to implement OSA testing in the standard work-up of AF patients are not provided in the guidelines. Additionally, overnight OSA monitoring rather than interrogation for OSA-related clinical signs alone may be necessary to reliably identify OSA in the majority of AF patients. This review summarizes the available clinical data on OSA in AF patients, and discusses the following key questions: Why and When is testing for OSA needed in AF patients? How and Where should it be performed and coordinated? and Who should test for OSA? To implement OSA testing in a cardiology or electrophysiology clinic, we propose a multidisciplinary integrated care approach based on a chronic care model. We describe the tools, infrastructure and coordination needed to test for OSA in the standard workup of patients with symptomatic AF prior to the initiation of directed invasive or pharmacological rhythm control management.

High prevalence of iatrogenic hyperthyroidism in elderly patients with atrial fibrillation in an anticoagulation clinic.

PubMed

Krishnan, Sandeep Kumar; Dohrmann, Mary L; Brietzke, Stephen A; Fleming, David A; Flaker, Greg C

2011-01-01

In elderly patients with established atrial fibrillation (AF) who are receiving thyroid replacement, regular testing for thyroid function is often not performed, placing the patient at risk for iatrogenic hyperthyroidism. Of 215 patients followed in an anticoagulation clinic, 41 were receiving thyroid replacement and 15 of these were found to have hyperthyroidism. Eight had documented AF coincident with abnormal thyroid function. In addition, only 22 patients on thyroid replacement had an annual TSH. In conclusion, iatrogenic hyperthyroidism may frequently be missed in AF patients because of inadequate monitoring of serum TSH. Thyroid replacement is common in elderly patients with AF followed in an anticoagulation clinic. Laboratory evidence of hyperthyroidism occurred in 37%, usually in patients with higher doses of thyroid replacement, and often associated with AF. The frequency of iatrogenic hyperthyroidism may be underestimated in patients with AF since many patients who receive thyroid replacement therapy are not monitored regularly with serum TSH.

Effect of aldosterone on cochlear Af9 expression and hearing in guinea pig.

PubMed

Qin, Li; Zhang, Biyun; Wang, Qianying; Li, Duanchao; Luo, Xiaoli; Zhong, Shixun

2017-09-01

Af9 protein in cochlea may be closely related to endolymph regulation by aldosterone and thus may be involved in pathogenesis of endolymphatic hydrops (EH). EH is the pathological characteristic of Ménière's disease (MD). Aldosterone could induce EH, but its relationship with MD is still controversial. The aim of the present study is to investigate the Af9 protein expression in guinea pig cochlea and regulation of Af9 expression and cochlear function by aldosterone. The role of Af9 in pathogenesis of EH is discussed. Thirty guinea pigs were randomly divided into two groups. The treatment group was intraperitoneally injected with aldosterone 0.1 mg/kg/d for 5 days, while the control group was done with saline. Hearing and histomorphology of cochlea were examined. In addition, expression of Af9 protein was studied. The hearing threshold of the treatment group was increased. EH was induced in 73% of guinea pigs in the treatment group, and no EH was found in the control group. Af9 protein was found in spiral limbus, stria vascularis, Reissner's membrane, organ of Corti and spiral ganglion in both groups. Af9 expression in cochlea decreased significantly at protein level after treatment by aldosterone.

Survey of Antithrombotic Treatment in Rural Patients (>60 years) with Atrial Fibrillation in East China.

PubMed

Wei, Yong; Xu, Juan; Wu, Haiqing; Zhou, Genqing; Chen, Songwen; Wang, Caihong; Shen, Yahong; Yang, Shunhong; Wang, Bin; He, Zheng; Sun, Jianping; Sun, Weidong; Ouyang, Ping; Liu, Shaowen

2018-05-01

The prevalence and antithrombotic treatment of atrial fibrillation (AF) in Chinese rural population is not well known. The aim of this study was to investigate the extent to which antithrombotic treatment was prescribed for rural AF patients >60 years. We identified 828 AF patients from 36734 rural residents >60 years in Shanghai China. Our data indicated the overall prevalence rate of AF was 2.3% in rural population >60 years in East China and 38.9% of AF patients underwent antithrombotic therapy, including warfarin (5.9%), aspirin (29.6%), clopidogrel (2.9%) and aspirin combined with clopidogrel (0.5%). Of enrolled subjects, 98.4% had CHA 2 DS 2 -VASc score ≥1, 72.0% had HAS-BLED score <3 and 59.2% had CHA 2 DS 2 -VASc score ≥2 with HAS-BLED score <3. Missing early detection (34.9%), delay in seeking treatment for asymptomatic AF (25.5%) and doctors's incomplete inform of AF-related risk of stroke to patients (21.7%) were three dominant causes for failing anticoagulant usage. In conclusion, most AF patients were with a high risk of thrombosis and a low risk of bleeding in China, but a large majority of them failed to take anticoagulants mainly for missing an early screening of AF and lack of awareness on AF for both patients and primary care physicians.

GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

PubMed

Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

2014-01-01

The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

Factors associated with a poor prognosis for the IVF-ICSI live birth rate in women with rAFS stage III and IV endometriosis.

PubMed

Roux, Pauline; Perrin, Jeanne; Mancini, Julien; Agostini, Aubert; Boubli, Léon; Courbiere, Blandine

2017-07-01

To assess the factors associated with a poor prognosis for a cumulative IVF live birth rate (LBR) in women with stage III and IV endometriosis according to the revised classification of the American Fertility Society (rAFS). A retrospective cohort study was conducted between January 1, 2010, and December 31, 2014, in our Reproductive Medicine Center. We analyzed different factors associated with a poor prognosis for a cumulative IVF LBR in women with rAFS stage III and IV endometriosis. A total of 101 patients were included, representing 232 IVF-ICSI cycles and 212 embryo transfers. The primary endpoint was the cumulative LBR per cycle and per patient. The cumulative LBR per cycle was 14.7% (n = 34) and that per patient was 31.7% (n = 32). The cumulative LBR was significantly decreased by active smoking [ adj OR = 3.4, 95% CI (1.12-10.60), p = 0.031], poor ovarian response (POR) according to the Bologna criteria [ adj OR = 11.5, 95% CI (1.37-96.83), p = 0.024], and rAFS stage IV [ adj OR = 3.2, 95% CI (1.13-8.95), p = 0.024]. The cumulative LBR per women was 59.4% without factors associated with a poor prognosis and 25.6% in the case of one factor, and it decreased to 7.7% in the case of two or three factors (p < 0.001). Active smoking, POR according to the Bologna criteria, and rAFS stage IV endometriosis had a negative impact on the IVF-ICSI cumulative LBR for women with rAFS stage III and IV endometriosis. Because smoking dramatically decreases the LBR with endometriosis, stopping smoking before IVF-ICSI should be strongly advised.

Improving atrial fibrillation detection in patients with implantable cardiac devices by means of a remote monitoring and management application.

PubMed

Zoppo, Franco; Facchin, Domenico; Molon, Giulio; Zanotto, Gabriele; Catanzariti, Domenico; Rossillo, Antonio; Baccillieri, Maria Stella; Menard, Cecile; Comisso, Jennifer; Gentili, Alessandra; Grammatico, Andrea; Bertaglia, Emanuele; Proclemer, Alessandro

2014-12-01

Atrial fibrillation (AF) is common in patients with cardiac implantable electronic devices (CIED) and has been associated with an increased stroke risk. The aim of our project was to assess the clinical value of a web-based application, Discovery Link AFinder, in improving AF detection in CIED patients. Seven Italian hospitals performed an observational study consisting of four phases. During phase 1, expert nurses and cardiologists prospectively followed-up CIED patients via in-hospital examinations and remote monitoring, and classified clinically relevant events, particularly AF occurrence. During phase 2, Discovery Link AFinder was exploited to identify patients who had suffered AF in the previous 12 months through the systematic scanning of device data remote transmissions. Phases 3 and 4 were repetitions of phases 1 and 2, respectively, and were implemented 6 months after the previous phases. A total of 472 consecutive patients were included in phase 1; AF occurred in 170 patients, 61 of whom were identified as new AF patients. Evidence of AF during this phase prompted prescription of oral anticoagulation (OAC) therapy in 30 patients. In phase 2, AFinder uncovered new AF, unidentified in phase 1, in 54 patients and prompted implementation of OAC therapy in 11 patients. During phase 3, 30 new AF patients were identified by means of remote monitoring, while during phase 4, a further three AF patients were identified by AFinder only. The AFinder web-based software, applied on top of standard in-hospital and remote monitoring, improved AF detection and enabled OAC treatment to be undertaken. ©2014 Wiley Periodicals, Inc.

Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients

PubMed Central

Leichtweis, Gustavo Elias; Andriolo, Luiza; Delevatti, Yasmim A.; Jorge, Amaury C.; Fumagalli, Andreia C.; Santos, Luiz Claudio; Miura, Cecilia K.; Saito, Sergio K.

2017-01-01

Background Acute Atrial Fibrillation (AF) is common in critically ill patients, with significant morbidity and mortality; however, its incidence and severity in Intensive Care Units (ICUs) from low-income countries are poorly studied. Additionally, impact of vasoactive drugs on its incidence and severity is still not understood. This study aimed to assess epidemiology and risk factors for acute new-onset AF in critically ill adult patients and the role of vasoactive drugs. Method Cohort performed in seven general ICUs (including cardiac surgery) in three cities in Paraná State (southern Brazil) for 45 days. Patients were followed until hospital discharge. Results Among 430 patients evaluated, the incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was correlated with higher incidence of AF and higher mortality in patients with AF; vasopressin (though used in few patients) had no effect on development of AF. Conclusions In general ICU patients, incidence of new-onset AF was 11.2% with a high impact on morbidity and mortality, particularly associated with the presence of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity and mortality. PMID:28702263

Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients.

PubMed

Duarte, Péricles A D; Leichtweis, Gustavo Elias; Andriolo, Luiza; Delevatti, Yasmim A; Jorge, Amaury C; Fumagalli, Andreia C; Santos, Luiz Claudio; Miura, Cecilia K; Saito, Sergio K

2017-01-01

Acute Atrial Fibrillation (AF) is common in critically ill patients, with significant morbidity and mortality; however, its incidence and severity in Intensive Care Units (ICUs) from low-income countries are poorly studied. Additionally, impact of vasoactive drugs on its incidence and severity is still not understood. This study aimed to assess epidemiology and risk factors for acute new-onset AF in critically ill adult patients and the role of vasoactive drugs. Cohort performed in seven general ICUs (including cardiac surgery) in three cities in Paraná State (southern Brazil) for 45 days. Patients were followed until hospital discharge. Among 430 patients evaluated, the incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was correlated with higher incidence of AF and higher mortality in patients with AF; vasopressin (though used in few patients) had no effect on development of AF. In general ICU patients, incidence of new-onset AF was 11.2% with a high impact on morbidity and mortality, particularly associated with the presence of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity and mortality.

Comparing the economic burden of ischemic stroke patients with and without atrial fibrillation: a retrospective study in Beijing, China.

PubMed

Wen, Liankui; Wu, Jingjing; Feng, Lin; Yang, Li; Qian, Feng

2017-10-01

Little is known about the economic burden for ischemic stroke (IS) patients with atrial fibrillation (AF) in China. We aimed to compare the economic burden of treatment-related costs in IS patients with AF vs. without AF in China. This retrospective analysis used economic burden data from the Beijing urban health insurance database. Using a random sampling method, 10% of the patients diagnosed with IS from 1 January through 31 December 2012 were enrolled. First hospitalization was considered as the index event and hospital utilization after the index event was followed up until September 2013. Overall healthcare cost during the study period was analyzed. In 4061 patients with IS (mean ± SD age, 68.45 ± 13.95 years; AF: 992; without AF: 3069), the AF group had a higher percentage of patients with co-morbidities at baseline. Compared with the non-AF group, the AF group had significantly greater hospitalization at the index event (p < .001). Overall inpatient cost per patient during the observational period (Renminbi (RMB) 141,875.9 ± 121,071.8 vs. RMB 53,834.03 ± 63,535.72, in 2012 terms), total healthcare cost per patient (RMB 163,550.4 ± 131,103.5 vs. RMB 64,735.41 ± 67,584.95), total healthcare cost covered by health insurance, and annualized total healthcare cost per patient were higher in the AF group than in the non-AF group (p < .001). Treatment costs were significantly associated with old age, male gender, AF, and frequency of outpatient visits and hospitalization. AF increased the use of healthcare resources, treatment cost, and economic burden in patients with IS. Therefore, prevention of cardio-embolic events in patients with AF by anticoagulants may decrease the economic burden in patients with IS.

Direct thrombin and factor Xa inhibition for stroke prevention in patients with atrial fibrillation.

PubMed

Galanis, Taki; Merli, Geno J

2013-02-01

Nonvalvular atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia occurring in patients in the United States. The primary clinical consequence of AF is an increase in the risk and severity of strokes. Treatment guidelines recommend anticoagulation therapy for most patients with AF. One risk-stratification scheme, the CHADS2 index, is simple and widely used to determine the management of patients with AF in regard to stroke prevention. However, new schemes, such as CHA2DS2-VASc, further refine risk stratification to identify patients who would obtain a net clinical benefit from a particular management strategy, thus improving the quality of management. For patients with AF for whom oral anticoagulation (OAC) is advisable, vitamin K antagonist (VKA) therapy is well established and effective. However, OAC with VKAs presents challenges to prescribers and patients in maintaining therapeutic efficacy. Novel OACs may offer alternatives to VKAs. Dabigatran etexilate, a direct thrombin inhibitor, was approved by the US Food and Drug Administration (FDA) in 2010 for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. The activated factor X (factor Xa) inhibitor rivaroxaban was recently approved by the FDA both for prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip arthroplasty, and for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. Apixaban, another factor Xa inhibitor, was recently shown to be effective for stroke prevention in patients with nonvalvular AF. This article reviews clinical considerations regarding new agents that may offer alternatives to VKA therapy for the prevention of stroke in patients with AF.

Quality of life with atrial fibrillation: do the spouses suffer as much as the patients?

PubMed

Bohnen, Marius; Shea, Julie B; Michaud, Gregory F; John, Roy; Stevenson, William G; Epstein, Laurence M; Tedrow, Usha B; Albert, Christine; Koplan, Bruce A

2011-07-01

Atrial fibrillation (AF) can have a significant effect on quality of life (QoL). Other chronic diseases are known to not only affect the patient but to also impact the QoL of persons living with them. Scant data exist on the QoL effect of AF in spouses/significant others (SOs). An anonymous survey regarding the perceived effect of AF on QoL was designed and distributed to both patients and spouses/SOs during an educational symposium about living with AF. Both were asked to fill out the survey independently according to how their life was affected by either their AF or their partner's AF. Questions included demographics, perceived impairment of overall QoL on a 5-point scale, as well as effect on subcategories of QoL, namely daily activity, work life, sex life, physical activity, psychological well-being, and social activity. Five hundred and sixty-eight subjects completed the survey of which 411 were AF patients and 129 were spouses/SOs. The perceived effect of AF on overall QoL (N = 527) was similar in patients and spouses (AF patients: mild 42.0%, moderate 26.0%, severe 32.0% vs. spouses: 44.1%, 25.2%, 31.7%; P = 0.917). This result did not change when adjusted for age and gender. There was also no significant difference between patients and spouses in the subcategories of QoL with the exception of the perceived effect on work life, which was greater in patients than spouses (P = 0.041). AF has a similar perceived impact on the QoL of spouses and patients. QoL improvement strategies for patients with AF should take spouses into account. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

The prognostic significance of cardiac structure and function in atrial fibrillation: the ENGAGE AF-TIMI 48 Echocardiographic Substudy

PubMed Central

Gupta, Deepak K; Giugliano, Robert P; Ruff, Christian T; Claggett, Brian; Murphy, Sabina; Antman, Elliott; Mercuri, Michele F.; Braunwald, Eugene; Solomon, Scott D

2016-01-01

Background Atrial fibrillation (AF) is associated with increased risk for thromboembolism and death; however, the relationships between cardiac structure and function and adverse outcomes among individuals with AF are incompletely understood. Methods The ENGAGE AF –TIMI 48 study tested the once-daily oral factor Xa inhibitor edoxaban in comparison to warfarin for the prevention of stroke (ischemic or hemorrhagic) or systemic embolism in 21,105 subjects with nonvalvular AF and increased risk for thromboembolic events (CHADS2 ≥ 2). In a prospective substudy of 971 subjects who underwent transthoracic echocardiography at baseline, we used Cox proportional hazards models to evaluate the associations between cardiac structure and function and the risks for death and thromboembolism (ischemic stroke, TIA, or systemic embolism). Results Over a median follow up of 2.5 years, 89 (9.2%) deaths and 48 (4.9%) incident thromboembolic events occurred in 971 subjects. In models adjusted for CHADS2 score, aspirin use, and randomized treatment, larger LV end diastolic volume index (HR: 1.49 [95%CI: 1.16,1.91] per 1 SD [12.9 ml/m2]) and higher LV filling pressures measured by E/′e (HR: 1.32 [95%CI: 1.08,1.61] per 1 SD [4.6]) were independently associated with increased risks for death. E/e′ > 13 significantly improved prediction of death beyond clinical factors alone. No features of cardiac structure and function were independently associated with thromboembolism in this population. Findings were similar when adjusted for CHA2DS2-VASc in place of CHADS2. Conclusions In a contemporary population of patients with atrial fibrillation at increased risk for thromboembolic events, larger LV size and higher filling pressures were significantly associated with increased risk for death, but neither left atrial nor left ventricular measures were associated with thromboembolic risk. LV size and filling pressures may help identify AF patients at increased risk of death. PMID:27106009

GPIM AF-M315E Propulsion System

NASA Technical Reports Server (NTRS)

Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

2014-01-01

The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

Risk Factors For Bradycardia Requiring Pacemaker Implantation In Patients With Atrial Fibrillation

PubMed Central

Barrett, Tyler W.; Abraham, Robert L.; Jenkins, Cathy A.; Russ, Stephan; Storrow, Alan B.; Darbar, Dawood

2012-01-01

Symptomatic bradycardia may complicate atrial fibrillation (AF) and necessitate a permanent pacemaker. Identifying patients at increased risk for symptomatic bradycardia may reduce associated morbidities and healthcare costs. We investigated predictors for developing bradycardia requiring a permanent pacemaker among AF patients. We reviewed records of all patients treated for AF/flutter in an academic hospital’s emergency department from 8/1/2005 to 8/30/2008. We determined survival and presence of a pacemaker as of 11/1/2011. Cases were defined as patients with pacemakers placed for bradycardia after their AF diagnoses. Patients without a pacemaker who were followed at our hospital comprised the controls. We identified a priori variables for the logistic regression analysis. We fit a post-hoc model adjusting for AF type and atrioventricular nodal blocker (AVN) use. Of the 362 patients in our cohort, 119 cases had permanent pacemakers implanted for bradycardia subsequent to AF diagnosis and 243 controls were alive without a pacemaker. Median and interquartile range follow-up time was 4.5 (3.8 – 5.4) years. Odds ratios and 95% confidence intervals were determined for age at time of AF diagnosis (1.02 [1, 1.04]), female (1.58 [0.95, 2.63]), prior heart failure (2.72 [1.47, 5.01]), and African-American (0.33 [0.12, 0.94]). Post-hoc model identified permanent AF (2.99 [1.61, 5.57]) and AVN use (1.43 [0.85, 2.4]). In conclusion, among AF patients, heart failure and permanent AF each nearly triple the odds of developing bradycardia requiring a permanent pacemaker; while not statistically significant, our results suggest that women are more likely and African-Americans less likely to develop bradycardia requiring pacemaker implantation. PMID:22840846

Comprehensive Mutation Scanning of LMNA in 268 Patients With Lone Atrial Fibrillation

PubMed Central

Brauch, Katharine M.; Chen, Lin Y.; Olson, Timothy M.

2009-01-01

Atrial fibrillation (AF) is a heritable, genetically heterogeneous disorder. To identify gene defects that cause or confer susceptibility to AF, a cohort of 268 unrelated patients with idiopathic forms of familial and sporadic AF was recruited. LMNA, encoding the nuclear membrane proteins, lamin A/C, was selected as a candidate gene for lone AF based on its established association with a syndrome of dilated cardiomyopathy, conduction system disease, and AF. Comprehensive mutation scanning identified only 1 potentially pathogenic mutation. In conclusion, LMNA mutations rarely cause lone AF and routine genetic testing of LMNA in these patients does not appear warranted. PMID:19427440

Catheter ablation in patients with persistent atrial fibrillation

PubMed Central

Kirchhof, Paulus; Calkins, Hugh

2017-01-01

Catheter ablation is increasingly offered to patients who suffer from symptoms due to atrial fibrillation (AF), based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy. Approximately one-third of AF ablation procedures are currently performed in patients with persistent or long-standing persistent AF. Here, we review the available information to guide catheter ablation in these more chronic forms of AF. We identify the following principles: Our clinical ability to discriminate paroxysmal and persistent AF is limited. Pulmonary vein isolation is a reasonable and effective first approach for catheter ablation of persistent AF. Other ablation strategies are being developed and need to be properly evaluated in controlled, multicentre trials. Treatment of concomitant conditions promoting recurrent AF by life style interventions and medical therapy should be a routine adjunct to catheter ablation of persistent AF. Early rhythm control therapy has a biological rationale and trials evaluating its value are underway. There is a clear need to generate more evidence for the best approach to ablation of persistent AF beyond pulmonary vein isolation in the form of adequately powered controlled multi-centre trials. PMID:27389907

Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography.

PubMed

Abidov, Aiden; Hachamovitch, Rory; Rozanski, Alan; Hayes, Sean W; Santos, Marcia M; Sciammarella, Maria G; Cohen, Ishac; Gerlach, James; Friedman, John D; Germano, Guido; Berman, Daniel S

2004-09-01

The aim of this research was to determine whether presence of atrial fibrillation (AF) provides incremental prognostic information relative to myocardial perfusion single-photon emission computed tomography (MPS) with respect to risk of cardiac death (CD). The prognostic significance of AF in patients undergoing MPS is not known. A total of 16,048 consecutive patients undergoing MPS were followed-up for a mean of 2.21 +/- 1.15 years for the development of CD. Of those, 384 patients (2.4%) had AF. Cox proportional hazards method was used to compare clinical and perfusion data for the prediction of CD in patients with and without AF. Atrial fibrillation was a significant predictor of CD in patients with normal (1.6% per year vs. 0.4% per year in non-AF patients), mildly abnormal (6.3% per year vs. 1.2% per year), and severely abnormal MPS (6.4% per year vs. 3.7% per year) (p < 0.001 for all). By multivariable analysis, AF patients had worse survival (p = 0.001) even after adjustment for the variables most predictive of CD: age, diabetes, shortness of breath, use of vasodilator stress, rest heart rate, and the nuclear variables. In the 4,239 patients with left ventricular ejection fraction evaluated by gated MPS, AF demonstrated incremental prognostic value not only over clinical and nuclear variables, but also over left ventricular ejection in predicting CD (p = 0.014). The presence of AF independently increases the risk of cardiac events over perfusion and function variables in patients undergoing MPS. Patients with AF have a high risk of CD, even when MPS is only mildly abnormal. Whether patients with AF and mildly abnormal MPS constitute a group more deserving of early referral to cardiac catheterization is a question warranting further study.

Action of AF64A on rat brain muscarinic receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eva, C.; Costa, E.

ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased butmore » its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.« less

Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Atrial Fibrillation.

PubMed

Kumar, Sanjay; Qu, Sarah; Kassotis, John T

2012-01-01

Atrial fibrillation (AF) is the most common sustained atrial arrhythmia conferring a higher morbidity and mortality. Despite the increasing incidence of AF; available therapies are far from perfect. Dietary fish oils, containing omega 3 fatty acids, also called polyunsaturated fatty acid [PUFA] have demonstrated beneficial electrophysiological, autonomic and anti-inflammatory effects on both atrial and ventricular tissue. Multiple clinical trials, focusing on various subsets of patients with AF, have studied the role of PUFA and their potential role in reducing the incidence of this common arrhythmia. While PUFA appears to have a beneficial effect in the primary prevention of AF in the elderly with structural heart disease, this benefit has not been universally observed. In the secondary prevention of AF, PUFA seems to have a greater impact in the reducing AF in patients with paroxysmal or persistent AF, stages of AF associated with less atrial fibrosis and negative structural remodeling. However, AF suppression has not been consistently demonstrated in clinical trials. In patients undergoing heart surgery, increasing PUFA intake has yielded mixed results in terms of AF prevention post-operatively; however, increased PUFA has been associated with a reduction in hospital stay. Therefore recommending the use of PUFA for the purpose of AF reduction remains controversial. This is in part attributable to the complexity of AF. Other conflicting variables include: heterogeneous patient populations studied; variable dosing; duration of follow-up; comorbidities; and, concomitant pharmacotherapy. This review article reviews in detail available basic and clinical research studies of fish oil in the treatment of AF, and its role in the treatment of this common disorder. AF=Atrial fibrillation, CHS=Cardiovascular Health Study,CABG=Coronary artery bypass surgery, d=Day, DHA=Docosahexaenoic acid, EPA=Eicosapentaenoic acid, ERP= Effective refractory period, g=Gram, PAF= Paroxysmal

Aldosterone and renin in cardiac patients referred for catheterization.

PubMed

Erne, Paul; Müller, Andrea; Rossi, Gian Paolo; Seifert, Burkhardt; Stehlin, Fabrice; Redondo, Maurice; Bauer, Peter T; Kobza, Richard; Resink, Therese J; Radovanovic, Dragana

2017-06-01

Little is known regarding alterations of the renin-angiotensin system in patients referred for cardiac catheterization. Here, we measured plasma levels of active renin and aldosterone in patients referred for cardiac catheterization in order to determine the prevalence of elevated renin, aldosterone, and the aldosterone-renin ratio.A chemiluminescence assay was used to measure plasma aldosterone concentration (PAC) and active renin levels in 833 consecutive patients, after an overnight fasting and without any medication for least 12 hours. We evaluated associations of the hormonal elevations in relation to hypertension, atrial fibrillation (AF), hypertensive cardiomyopathy, coronary artery disease (CAD), valvular disease, impaired left ventricular ejection fraction (LVEF < 35%), and pulmonary hypertension (arterial pulmonary mean pressure >25 mm Hg).Hyperaldosteronism occurred in around one-third of all examined patients, without significant differences between patients with or without the named cardiac diseases. In a comparison between patients with or without any given cardiac disease condition, renin was significantly elevated in patients with either hypertension (36.4% vs 15.9%), CAD (33.9% vs 22.1%), or impaired LVEF (47.3% vs 24.8%). The angiotensin-renin ratio was elevated in AF patients and in patients with hypertensive cardiomyopathy. Patients with AF and coexisting hypertension had elevated renin more frequently than AF patients without coexisting hypertension (35.3% vs 16.5%; P  =  .005). Patients with persistent/permanent AF more frequently had elevated renin than patients with paroxysmal AF (34.1% vs 15.8%; P  =  .007).This prospective study of consecutive cardiac disease patients referred for cardiac catheterization has revealed distinct cardiac disease condition-associated differences in the frequencies of elevations in plasma renin, PAC, and the aldosterone-renin ratio.

The Bcr Kinase Downregulates Ras Signaling by Phosphorylating AF-6 and Binding to Its PDZ Domain

PubMed Central

Radziwill, G.; Erdmann, R. A.; Margelisch, U.; Moelling, K.

2003-01-01

The protein kinase Bcr is a negative regulator of cell proliferation and oncogenic transformation. We identified Bcr as a ligand for the PDZ domain of the cell junction and Ras-interacting protein AF-6. The Bcr kinase phosphorylates AF-6, which subsequently allows efficient binding of Bcr to AF-6, showing that the Bcr kinase is a regulator of the PDZ domain-ligand interaction. Bcr and AF-6 colocalize in epithelial cells at the plasma membrane. In addition, Bcr, AF-6, and Ras form a trimeric complex. Bcr increases the affinity of AF-6 to Ras, and a mutant of AF-6 that lacks a specific phosphorylation site for Bcr shows a reduced binding to Ras. Wild-type Bcr, but not Bcr mutants defective in binding to AF-6, interferes with the Ras-dependent stimulation of the Raf/MEK/ERK pathway. Since AF-6 binds to Bcr via its PDZ domain and to Ras via its Ras-binding domain, we propose that AF-6 functions as a scaffold-like protein that links Bcr and Ras to cellular junctions. We suggest that this trimeric complex is involved in downregulation of Ras-mediated signaling at sites of cell-cell contact to maintain cells in a nonproliferating state. PMID:12808105

Effect of hyperthyroidism on the hypercoagulable state and thromboembolic events in patients with atrial fibrillation.

PubMed

Chen, Qingxing; Yan, Yan; Zhang, Lei; Cheng, Kuan; Liu, Yuping; Zhu, Wenqing

2014-01-01

To clarify whether hyperthyroidism (HT) itself confers an additional effect on the hypercoagulable state and the risk of ischemic stroke among patients with hyperthyroid atrial fibrillation (AF). We prospectively evaluated plasma D-dimer levels and thromboembolic events among three groups of patients (hyperthyroid AF, n = 62; nonthyroid AF, n = 107, and HT without AF, n = 100). Plasma D-dimer levels were used to evaluate the hypercoagulable state. The D-dimer level was significantly higher in patients with hyperthyroid AF than in nonthyroid AF (0.66 ± 0.06 vs. 0.34 ± 0.02 mg/l, p < 0.001) and HT without AF (0.66 ± 0.06 vs. 0.27 ± 0.02 mg/l, p < 0.001). During a 3-year follow-up, patients with hyperthyroid AF had a significantly higher incidence of ischemic stroke compared with patients with nonthyroid AF (hazard ratio, HR: 3.2, 95% confidence interval, CI: 1.01-5.59, p = 0.04). Cox regression analysis revealed that age (HR: 2.5, 95% CI: 1.01-1.21, p = 0.05), CHADS2-VAS score (HR: 5.5, 95% CI: 1.51-7.43, p = 0.01) and anticoagulation (HR: 0.45, 95% CI: 0.07-0.54, p = 0.01) were independent predictors of risk for the occurrence of ischemic stroke. The present study suggests that HT may enhance the hypercoagulable state and the risk of ischemic stroke in patients with AF.

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.

PubMed

Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D; Hellkamp, Anne S; Piccini, Jonathan P; Stevens, Susanna R; Lokhnygina, Yuliya; Patel, Manesh R; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

2014-12-14

We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Many patients with 'non-valvular atrial fibrillation' have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

PubMed Central

Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D.; Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Halperin, Jonathan L.; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

2014-01-01

Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55–1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75–1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05–1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94–1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Conclusions Many patients with ‘non-valvular atrial fibrillation’ have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. PMID:25148838

Association Between Dehydration and Short-Term Risk of Ischemic Stroke in Patients with Atrial Fibrillation.

PubMed

Swerdel, Joel N; Janevic, Teresa M; Kostis, William J; Faiz, Ambarina; Cosgrove, Nora M; Kostis, John B

2017-04-01

Previous cross-sectional studies have demonstrated a higher incidence of dehydration in patients admitted for stroke suggesting a possible association. However, the temporality of the association has not been well established. We examined whether dehydration increases the risk of ischemic stroke in patients with a recent hospitalization for atrial fibrillation (AF). Data was from 1994 to 2012 from the Myocardial Infarction Data Acquisition System (MIDAS), a repository of in-patient records New Jersey hospitals, for AF hospitalizations (n = 1,282,787). Estimates for the association between AF hospitalization with/without dehydration and ischemic stroke within 30 days post-AF discharge were determined using log-linear multivariable modeling adjusting for socio-demographic factors and comorbid conditions. Within 10 days of discharge for AF, patients 18-80 years old (YO) with comorbid dehydration had a 60 % higher risk of ischemic stroke compared to AF patients without comorbid dehydration (adjusted risk ratio (ARR) 1.60, 95 % confidence interval (CI) 1.28-2.00). Eighteen- to 80-YO patients had a 34 % higher risk of ischemic stroke in days 11-20 post-AF discharge (ARR 1.34, 95 % CI 1.04, 1.74). There was no difference in the risk of stroke in 18-80-YO patients with or without prior dehydration during days 21-30 post-AF discharge. We also found no difference in the risk of ischemic stroke during any time period in patients over 80 YO. Dehydration may be a significant risk factor for ischemic stroke in patients 18-80 YO with AF.

The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR.

PubMed

Yang, Hua; Cao, Tingting; Gao, Li; Wang, Lili; Zhu, Chengying; Xu, Yuanyuan; Jing, Yu; Zhu, Haiyan; Lv, Na; Yu, Li

2017-07-20

Occurrence of MLL (Mixed Lineage Leukemia) gene rearrangements indicates poor prognosis in acute myeloid leukemia (AML) patients. This is the first study to report the positive rate and distribution characteristics of MLL rearrangements in AML patients in north China. We used multiplex nested real time PCR (RT-PCR) to screen for incidence of 11 MLL rearrangements in 433 AML patients. Eleven MLL rearrangements included (MLL-PTD, MLL-AF9, MLL-ELL, MLL-AF10, MLL-AF17, MLL-AF6, MLL-ENL, MLL-AF1Q, MLL-CBP, MLL-AF1P, MLL-AFX1). There were 68 AML patients with MLL rearrangements, and the positive rate was 15.7%. MLL-PTD (4.84%) was detected in 21 patients, MLL-AF9 in 15, (3.46%), MLL-ELL in 10 (2.31%), MLL-AF10 in 8 (1.85%), MLL-AF1Q in 2 (0.46%), 3 cases each of MLL-AF17, MLL-AF6, MLL-ENL (0.69% each), a and single case each of MLL-CBP, MLL-AF1P, and MLL-AFX1 (0.23% each). The highest rate of MLL rearrangements was found in 24 patients with M5 subtype AML, occurring in 24 cases (35.3%). MLL rearrangements occurred in 21 patients with M2 subtype AML (30.9%), and in 10 patients with M4 subtype AML (14.7%). Screening fusion genes by multiplex nested RT-PCR is a convenient, fast, economical, and accurate method for diagnosis and predicting prognosis of AML.

On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF.

PubMed

Fordyce, Christopher B; Hellkamp, Anne S; Lokhnygina, Yuliya; Lindner, Samuel M; Piccini, Jonathan P; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Mahaffey, Kenneth W; Nessel, Christopher C; Singer, Daniel E; Patel, Manesh R

2016-07-05

Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin. After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On-treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models. Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban. Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an

Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients?

PubMed

Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Santa Clara, Helena; Portugal, Guilherme; Gonçalves Rodrigues, Inês; Santos, Vanessa; Morais, Luís; Selas, Mafalda; Soares, Rui; Branco, Luísa; Ferreira, Rui; Mota Carmo, Miguel

2017-10-01

The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR). We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO 2 max) and ventilatory efficiency (VE/VCO 2 slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device. All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO 2 max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO 2 max (p=0.001; 0.083 age-adjusted) showed larger increases. Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients (ClinicalTrials.gov identifier: NCT02413151; FCT code: PTDC/DES/120249/2010). Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

The Impact of Transforming Growth Factor-β1 Level on Outcome After Catheter Ablation in Patients With Atrial Fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2017-04-01

Transforming growth factor-β 1 (TGF-β 1 ) is an important factor that induces atrial fibrosis and atrial fibrillation (AF). The purpose of this study was to evaluate the association between TGF-β 1 level and clinical factors before catheter ablation (CA), and to investigate the impact of TGF-β 1 level on the outcome after CA for AF. This prospective study included 151 patients (persistent AF group: n = 59, paroxysmal AF [PAF] group: n = 54, and control group: n = 38). All patients who underwent CA for AF were followed up for 12 months. The PAF group had the highest TGF-β 1 levels in all patients. An early recurrence of AF (ERAF: defined as episodes of atrial tachyarrhythmia within a 3-month blanking period) was detected in 60 patients (53%). Recurrent AF after the blanking period was detected in 36 patients (32%). On multivariate analysis, low TGF-β 1 level was the only independent factor associated with recurrent AF. Moreover, the AF recurrence ratio was higher in the low TGF-β 1 group (< 12.56 ng/mL) than in the high TGF-β 1 group (16 of 29 patients, 55% vs. 20 of 84 patients, 24%, P = 0.002 by log-rank test). PAF was associated with a higher TGF-β 1 level. Moreover, lower TGF-β 1 level in AF patients could be a cause of recurrent AF after CA. © 2017 Wiley Periodicals, Inc.

Combined Aspirin and Anticoagulant Therapy in Patients with Atrial Fibrillation

PubMed Central

So, Charlotte H.; Eckman, Mark H.

2016-01-01

Background The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. Objective (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Design and Participants Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Main Measures Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Key Results Of 948 patients receiving OAC, 430 (45%) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49% and 42% of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27% had a diagnosis of CAD and 14% had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn’t discontinued. A surprisingly large proportion of patients (22.8%) had no obvious indication for dual therapy. Conclusions Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or

Surgical RF ablation of atrial fibrillation in patients undergoing mitral valve repair for Barlow disease.

PubMed

Rostagno, Carlo; Droandi, G; Gelsomino, S; Carone, E; Gensini, G F; Stefàno, P L

2013-01-01

At present, limited experience exists on the treatment of atrial fibrillation (AF) in patients undergoing mitral valve repair (MVR) for Barlow disease. The aim of this investigation was to prospectively evaluate the radiofrequency ablation of AF in patients undergoing MVR for severe regurgitation due to Barlow disease. From January 1, 2007 to December 31, 2010, out of 85 consecutive patients with Barlow disease, 27 with AF underwent RF ablation associated with MVR. They were examined every 4 months in the first year after surgery and thereafter twice yearly. At follow-up, AF was observed in 4/25 (16.0%). NYHA (New York Heart Association) functional class improved significantly, with no patients in class III or IV (before surgery, 81.5% had been). Otherwise, among 58 patients in sinus rhythm, 6 (11%) developed AF during follow-up. No clinical or echocardiographic predictive factor was found in this subgroup. Results from our investigation suggest that radiofrequency ablation of AF in patients with Barlow disease undergoing MVR for severe regurgitation is effective and should be considered in every patient with Barlow disease and AF undergoing valve surgical repair. Copyright © 2013 S. Karger AG, Basel.

Improvements In AF Ablation Outcome Will Be Based More On Technological Advancement Versus Mechanistic Understanding.

PubMed

Jiang Md, Chen-Yang; Jiang Ms, Ru-Hong

2014-01-01

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Catheter ablation has proven more effective than antiarrhythmic drugs in preventing clinical recurrence of AF, however long-term outcome remains unsatisfactory. Ablation strategies have evolved based on progress in mechanistic understanding, and technologies have advanced continuously. This article reviews current mechanistic concepts and technological advancements in AF treatment, and summarizes their impact on improvement of AF ablation outcome.

Left atrial low-voltage areas predict atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

PubMed

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Matsuda, Yasuhiro; Okuno, Shota; Ohashi, Takuya; Tsuji, Aki; Mano, Toshiaki

2018-04-15

Association between the presence of left atrial low-voltage areas and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been shown mainly in persistent AF patients. We sought to compare the AF recurrence rate in paroxysmal AF patients with and without left atrial low-voltage areas. This prospective observational study included 147 consecutive patients undergoing initial ablation for paroxysmal AF. Voltage mapping was performed after PVI during sinus rhythm, and low-voltage areas were defined as regions where bipolar peak-to-peak voltage was <0.50mV. Left atrial low-voltage areas after PVI were observed in 22 (15%) patients. Patients with low-voltage areas were significantly older (72±6 vs. 66±10, p<0.0001), more likely to be female (68% vs. 32%, p=0.002), and had higher CHA 2 DS 2 -VASc score (2.5±1.5 vs. 1.8±1.3, p=0.028). During a mean follow-up of 22 (18, 26) months, AF recurrence was observed in 24 (16%) and 16 (11%) patients after the single and multiple ablation procedures, respectively. AF recurrence rate after multiple ablations was higher in patients with low-voltage areas than without (36% vs. 6%, p<0.001). Low-voltage areas were independently associated with AF recurrence even after adjustment for the other related factors (Hazard ratio, 5.89; 95% confidence interval, 2.16 to 16.0, p=0.001). The presence of left atrial low-voltage areas after PVI predicts AF recurrence in patients with paroxysmal AF as well as in patients with persistent AF. Copyright © 2017 Elsevier B.V. All rights reserved.

Aldosterone and renin in cardiac patients referred for catheterization

PubMed Central

Erne, Paul; Müller, Andrea; Rossi, Gian Paolo; Seifert, Burkhardt; Stehlin, Fabrice; Redondo, Maurice; Bauer, Peter T.; Kobza, Richard; Resink, Therese J.; Radovanovic, Dragana

2017-01-01

Abstract Little is known regarding alterations of the renin-angiotensin system in patients referred for cardiac catheterization. Here, we measured plasma levels of active renin and aldosterone in patients referred for cardiac catheterization in order to determine the prevalence of elevated renin, aldosterone, and the aldosterone-renin ratio. A chemiluminescence assay was used to measure plasma aldosterone concentration (PAC) and active renin levels in 833 consecutive patients, after an overnight fasting and without any medication for least 12 hours. We evaluated associations of the hormonal elevations in relation to hypertension, atrial fibrillation (AF), hypertensive cardiomyopathy, coronary artery disease (CAD), valvular disease, impaired left ventricular ejection fraction (LVEF < 35%), and pulmonary hypertension (arterial pulmonary mean pressure >25 mm Hg). Hyperaldosteronism occurred in around one-third of all examined patients, without significant differences between patients with or without the named cardiac diseases. In a comparison between patients with or without any given cardiac disease condition, renin was significantly elevated in patients with either hypertension (36.4% vs 15.9%), CAD (33.9% vs 22.1%), or impaired LVEF (47.3% vs 24.8%). The angiotensin-renin ratio was elevated in AF patients and in patients with hypertensive cardiomyopathy. Patients with AF and coexisting hypertension had elevated renin more frequently than AF patients without coexisting hypertension (35.3% vs 16.5%; P  =  .005). Patients with persistent/permanent AF more frequently had elevated renin than patients with paroxysmal AF (34.1% vs 15.8%; P  =  .007). This prospective study of consecutive cardiac disease patients referred for cardiac catheterization has revealed distinct cardiac disease condition-associated differences in the frequencies of elevations in plasma renin, PAC, and the aldosterone-renin ratio. PMID:28640140

Exchange bias mechanism in FM/FM/AF spin valve systems in the presence of random unidirectional anisotropy field at the AF interface: The role played by the interface roughness due to randomness

NASA Astrophysics Data System (ADS)

Yüksel, Yusuf

2018-05-01

We propose an atomistic model and present Monte Carlo simulation results regarding the influence of FM/AF interface structure on the hysteresis mechanism and exchange bias behavior for a spin valve type FM/FM/AF magnetic junction. We simulate perfectly flat and roughened interface structures both with uncompensated interfacial AF moments. In order to simulate rough interface effect, we introduce the concept of random exchange anisotropy field induced at the interface, and acting on the interface AF spins. Our results yield that different types of the random field distributions of anisotropy field may lead to different behavior of exchange bias.

Comparison of C-reactive protein levels in patients who do and do not develop atrial fibrillation during electrophysiologic study.

PubMed

Pirat, Bahar; Atar, Ilyas; Ertan, Cagatay; Bozbas, Huseyin; Gulmez, Oyku; Müderrisoglu, Haldun; Ozin, Bulent

2007-11-15

C-reactive protein (CRP) was increased in patients with atrial fibrillation (AF). The aim of this study was to evaluate CRP after inducing AF in 39 patients undergoing electrophysiologic study (EPS). After a diagnostic EPS, programmed atrial stimulation with 3 extra stimuli from the right atrium was performed in all patients. CRP was measured before and 6 and 24 hours after the procedure. Patients in whom AF was induced were monitored for 24 hours. AF was induced in 18 of 39 patients. Twenty-one patients without a tachyarrhythmia constituted the control group. Groups were similar with regard to age, gender, incidences of hypertension and diabetes, and history of coronary artery disease. On average, AF lasted 4.8 hours, and spontaneous conversion to sinus rhythm was observed in all patients. There were no statistically significant differences with respect to baseline and 6-hour CRP values between groups. However, mean CRP at 24 hours was significantly higher in patients with AF compared with controls (10 +/- 11 and 3.9 +/- 4.2 mg/L; p = 0.04). In conclusion, induction of AF during EPS led to increased CRP. This finding suggested that increased CRP may be the consequence of AF.

Does the STAF score help detect paroxysmal atrial fibrillation in acute stroke patients?

PubMed

Horstmann, S; Rizos, T; Güntner, J; Hug, A; Jenetzky, E; Krumsdorf, U; Veltkamp, R

2013-01-01

Detecting paroxysmal atrial fibrillation (pAF) soon after acute cerebral ischaemia has a major impact on secondary stroke prevention. Recently, the STAF score, a composite of clinical and instrumental findings, was introduced to identify stroke patients at risk of pAF. We aimed to validate this score in an independent study population. Consecutive patients admitted to our stroke unit with acute ischaemic stroke were prospectively enrolled. The diagnostic work-up included neuroimaging, neuroultrasound, baseline 12-channel electrocardiogram (ECG), 24-h Holter ECG, continuous ECG monitoring, and echocardiography. Presence of AF was documented according to the medical history of each patient and after review of 12-lead ECG, 24-h Holter ECG, or continuous ECG monitoring performed during the stay on the ward. Additionally, a telephone follow-up visit was conducted for each patient after 3 months to inquire about newly diagnosed AF. Items for each patient-age, baseline NIHSS, left atrial dilatation, and stroke etiology according to the TOAST criteria - were assessed to calculate the STAF score. Overall, 584 patients were enrolled in our analysis. AF was documented in 183 (31.3%) patients. In multivariable analysis, age, NIHSS, left atrial dilatation, and absence of vascular etiology were independent predictors for AF. The logistic AF-prediction model of the STAF score revealed fair classification accuracy in receiver operating characteristic curve analysis with an area under the curve of 0.84. STAF scores of ≥5 had a sensitivity of 79% and a specificity of 74% for predicting AF. The value of the STAF score for predicting the risk of pAF in stroke patients is limited. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Remodeling of Kv1.5 channel in right atria from Han Chinese patients with atrial fibrillation.

PubMed

Ou, Xian-hong; Li, Miao-ling; Liu, Rui; Fan, Xin-rong; Mao, Liang; Fan, Xue-hui; Yang, Yan; Zeng, Xiao-rong

2015-04-28

The incidence of atrial fibrillation (AF) in rheumatic heart diseases (RHD) is very high and increases with age. Occurrence and maintenance of AF are very complicated process accompanied by many different mechanisms. Ion-channel remodeling, including the voltage-gated potassium channel Kv1.5, plays an important role in the pathophysiology of AF. However, the changes of Kv1.5 channel expression in Han Chinese patients with RHD and AF remain poorly understood. The aim of the present study was to investigate whether the Kv1.5 channels of the right atria may be altered with RHD, age, and sex to contribute to AF. Right atrial appendages were obtained from 20 patients with normal cardiac functions who had undergone surgery, and 26 patients with AF. Subjects were picked from 4 groups: adult and aged patients in normal sinus rhythm (SR) and AF. Patients were divided into non-RHD and RHD groups or men and women groups in normal SR and AF, respectively. The expression of Kv1.5 protein and messenger RNA (mRNA) were measured using Western blotting and polymerase chain reaction (PCR) method, respectively. Compared with the SR group, the expression of Kv1.5 protein decreased significantly in the AF group. However, neither Kv1.5 protein nor KCNA5 mRNA had significant differences in adult and aged groups, non-RHD and RHD group, and men and women group of AF. The expression of Kv1.5 channel protein changes with AF but not with age, RHD, and sex in AF.

Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain.

PubMed

Zhang, Yejia; Chee, Ana; Shi, Peng; Adams, Sherrill L; Markova, Dessislava Z; Anderson, David Greg; Smith, Harvey E; Deng, Youping; Plastaras, Christopher T; An, Howard S

2016-06-01

To examine the link between cytokines in intervertebral disc (IVD) tissues and axial back pain. In vitro study with human IVD cells cultured from cadaveric donors and annulus fibrosus (AF) tissues from patients. Cultured nucleus pulposus (NP) and AF cells were stimulated with interleukin (IL)-1β. IL-8 and IL-7 gene expression was analyzed using real-time polymerase chain reaction. IL-8 protein was quantified by enzyme-linked immunosorbent assay. After IL-1β stimulation, IL-8 gene expression increased 26,541 fold in NP cells and 22,429 fold in AF cells, whereas protein released by the NP and AF cells increased 2,389- and 1,784-fold, respectively. IL-7 gene expression increased 3.3-fold in NP cells (P < 0.05).Cytokine profiles in AF tissues collected from patients undergoing surgery for back pain (painful group) or scoliosis (controls) were compared by cytokine array. IL-8 protein in the AF tissues from patients with back pain was 1.81-fold of that in controls. IL-7 and IL-10 in AF tissues from the painful group were 6.87 and 4.63 times greater than the corresponding values in controls, respectively (P < 0.05). Inflammatory mediators found in AF tissues from patients with discogenic back pain are likely produced by IVD cells and may play a key role in back pain.

Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts.

PubMed

Piccini, Jonathan P; Stevens, Susanna R; Chang, YuChiao; Singer, Daniel E; Lokhnygina, Yuliya; Go, Alan S; Patel, Manesh R; Mahaffey, Kenneth W; Halperin, Jonathan L; Breithardt, Günter; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Fox, Keith A A; Califf, Robert M

2013-01-15

We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2). In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients

[The clinical analysis of atrial fibrillation of 1 310 in patients in Urumqi of China].

PubMed

Guo, Xiaohua; Zhang, Yu; Xu, Guojun; Zhou, Xianhui; Li, Lei; Tang, Baopeng

2014-05-01

To investigate the clinical features and current therapy of atrial fibrillation (AF) of inpatients in Urumqi, China. The clinical data of inpatients diagnosed with AF from January, 2008 to December, 2012, in 12 hospitals in Urumqi were retrospectively analyzed. Totally 1 310 AF inpatients were enrolled in this study with the age of (64.8 ± 3.3) years old and a men to women ratio of 1.39. Most patients were in age groups of 61-70 years (26.5%) and 71-80 years (27.6%). More patients with paroxysmal AF were at cardiac function class I-II (75.2%), while more patients with persistent AF were at cardiac function class III-IV (31.0%) (both P values < 0.05). The most common co-morbidities of AF were hypertension (49.2%), coronary heart disease (38.5%), diabetes mellitus (20.1%). Compared with patients of chronic AF, the patients of paroxysmal AF had higher success rates in amiodarone conversation and sinus rhythm maintenance after ablation (44.8% vs 29.9%, 87.5% vs 68.9%, P values < 0.05). Among the 1 310 inpatients, 992 patients (75.7%) received antithrombotic therapy. There were statistically significant differences in CHA2DS2 score and incidence rate of cerebral infarction among patients receiving aspirin, warfarin or rivaroxaban/other anticoagulation drugs [2(1, 3) vs 3(2, 4) vs 3(2, 5) and 6.3% vs 23.8% vs 30.2%, both P values < 0.05]. Our results of AF inpatients' age, gender, related disease distribution, AF types, incidence of stoke, therapeutic and epidemiological features are in accordance with the domestic and abroad reports.

Relation between aphasia and arcuate fasciculus in chronic stroke patients

PubMed Central

2014-01-01

Background The role of the arcuate fasciculus (AF) in the dominant hemisphere in stroke patients with aphasia has not been clearly elucidated. We investigated the relation between language function and diffusion tensor tractography (DTT) findings for the left AF in chronic stroke patients with aphasia. Method Twenty five consecutive right-handed stroke patients with aphasia following lesions in the left hemisphere were recruited for this study. The aphasia quotient (AQ) of Korean-Western Aphasia Battery was used for assessment of language function. We measured values of fractional anisotropy (FA), apparent diffusion coefficient (ADC), voxel number of the left AF. We classified patients into three groups: type A - the left AF was not reconstructed, type B - the left AF was discontinued between Wernicke’s and Broca’s areas, and type C – the left AF was preserved around the stroke lesion. Results Moderate positive correlation was observed between AQ and voxel number of the left AF (r = 0.471, p < 0.05). However, no correlation was observed between AQ and FA (r = 0.275, p > 0.05) and ADC values (r = -0.286, p > 0.05). Significant differences in AQ scores were observed between the three types (p < 0.05); the AQ score of type C was higher than those of type A and B, and that of type B was also higher than that of type A (p < 0.05). Conclusion According to our findings, the remaining volume of the left AF, irrespective of directionality and diffusivity, showed moderate positive correlation with language function in chronic stroke patients with aphasia. Discontinuation or non-construction of the left AF was also an important factor for language function. PMID:24607148

Values and preferences for oral antithrombotic therapy in patients with atrial fibrillation: physician and patient perspectives.

PubMed

Alonso-Coello, Pablo; Montori, Victor M; Díaz, M Gloria; Devereaux, Philip J; Mas, Gemma; Diez, Ana I; Solà, Ivan; Roura, Mercè; Souto, Juan C; Oliver, Sven; Ruiz, Rafael; Coll-Vinent, Blanca; Gich, Ignasi; Schünemann, Holger J; Guyatt, Gordon

2015-12-01

Exploration of values and preferences in the context of anticoagulation therapy for atrial fibrillation (AF) remains limited. To better characterize the distribution of patient and physician values and preferences relevant to decisions regarding anticoagulation in patients with AF, we conducted interviews with patients at risk of developing AF and physicians who manage patients with AF. We interviewed 96 outpatients and 96 physicians in a multicenter study and elicited the maximal increased risk of bleeding (threshold risk) that respondents would tolerate with warfarin vs. aspirin to achieve a reduction in three strokes in 100 patients over a 2-year period. We used the probabilistic version of the threshold technique. The median threshold risk for both patients and physicians was 10 additional bleeds (10 P = 0.7). In both groups, we observed large variability in the threshold number of bleeds, with wider variability in patients than clinicians [patient range: 0-100, physician range: 0-50]. We observed one cluster of patients and physicians who would tolerate <10 bleeds and another cluster of patients, but not physicians, who would accept more than 35. Our findings suggest wide variability in patient and physician values and preferences regarding the trade-off between strokes and bleeds. Results suggest that in individual decision making, physician and patient values and preferences will often be discordant; this mandates tailoring treatment to the individual patient's preferences. © 2014 John Wiley & Sons Ltd.

Pre-clinical laboratory evaluation of the new 'AF' arterial line filter range.

PubMed

Yarham, Gemma; Mulholland, John

2010-07-01

The presence of emboli was recognised relatively early in the history of open heart surgery. The emboli produced during cardiopulmonary bypass have the predisposition to distribute into, and ultimately obstruct, microvessels of all tissues. The Sorin Group has recently developed a new range of arterial line filters. Before the Sorin AF range of filters was released for pre-launch clinical trials, our group performed in vitro laboratory testing of the AF range against a selection of commercially available filters on the global market. The Sorin AF620 and AF640 demonstrate both the smallest prime volume and smallest surface contact area (92ml and 290 cm(2), respectively).The results of the GME Handling Efficiency experiments ranged by 39.6%, from 95.9% to 56.3%. In terms of an air bolus handling, the results of the Limit Bolus experiment ranged by 97 ml, from 147.5 ml down to 50 ml. The pressure drop across all the filters was measured under steady state experimental conditions. All of the above investigations were considered against surface area and prime volume. It is clear from the results that some commercially available arterial line filters perform better than others, not only in overall performance, but also with regard to individual characteristics. Evaluating arterial line filters for hospital-specific use has to balance pressure drop, surface area, micro air handling, prime volume and gross air handling; all points need to be considered. In the AF620 and AF640, Sorin boast that they are the two smallest prime and smallest surface area filters commercially available on the global market. The Sorin AF filter range performs well in all of the areas we investigated and will be a competitive option for centres, irrespective of which characteristics they use to evaluate and select their arterial line filter.

Mast cell tryptase changes with Aspergillus fumigatus - Host crosstalk in cystic fibrosis patients.

PubMed

Gomez, Carine; Carsin, Ania; Gouitaa, Marion; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Mège, Jean-Louis; Ranque, Stéphane; Vitte, Joana

2018-02-15

Pulmonary and systemic antifungal immunity influences quality of life and survival of people with cystic fibrosis. Aspergillus fumigatus (Af) induces specific IgG and IgE. Mast cells respond to IgE, IgG and direct interactions with Af. Mast cells are the source of the protease tryptase. We aimed at evaluating serum baseline tryptase as a potential biomarker of the Af-host interaction in cystic fibrosis patients. Serum baseline tryptase, IgE and IgG directed to Af extract and Af molecular allergens were measured in 76 cystic fibrosis patients. The main findings were (i) lower levels of serum baseline tryptase in patients displaying specific IgE to Af (p < 0.0001) and (ii) an association between tryptase levels and IgE or IgG responses to Af and ribotoxin (Asp f 1). These findings suggest that serum baseline tryptase is influenced by Af-host interactions and thus might be a marker for mast cell regulation and pulmonary immune defenses. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Edoxaban vs warfarin in patients with nonvalvular atrial fibrillation in the US Food and Drug Administration approval population: An analysis from the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial.

PubMed

Eisen, Alon; Giugliano, Robert P; Ruff, Christian T; Nordio, Francesco; Gogia, Harinder S; Awasty, Vivek R; Henderson, David A; Mercuri, Michele F; Rutman, Howard; Antman, Elliott M; Braunwald, Eugene

2016-02-01

Edoxaban is a specific anti-Xa inhibitor that, in comparison to warfarin, has been found to be noninferior for the prevention of stroke or systemic embolism (SSE) and to reduce bleeding significantly in patients with nonvalvular atrial fibrillation (AF). The US Food and Drug Administration (FDA) approved the higher-dose edoxaban regimen (60/30 mg) in patients with AF and a creatinine clearance of ≤95 mL/min. We report for the first time the clinical characteristics, efficacy, and safety of the FDA-approved population in the ENGAGE AF--TIMI 48 trial. The patients included had been treated with either warfarin or edoxaban 60/30 mg and had a creatinine clearance of ≤95 mL/min. The primary efficacy was SSE, and the principal safety end point was major bleeding (International Society on Thrombosis and Haemostasis classification). Median follow-up was 2.8 years. Patients in the FDA-approved cohort were older, were more likely female, and had higher CHADS2 and HAS-BLED scores, as compared with patients not included in the FDA label. The primary end point occurred in 1.63%/y with edoxaban vs 2.02%/y with warfarin (hazard ratio [HR] 0.81, 95% CI 0.67-0.97, P = .023). Edoxaban significantly reduced the rate of hemorrhagic stroke (HR 0.47, 95% CI 0.31-0.72, P < .001) and cardiovascular death (HR 0.84, 95% CI 0.73-0.97, P = .015). Ischemic stroke rates were similar between the treatment groups (1.31%/y vs 1.39%/y, P = .97). Major bleeding was significantly lower with edoxaban (3.16%/y vs 3.77%/y; HR 0.84, 95% CI 0.72-0.98, P = .023). In the FDA-approved cohort of the ENGAGE AF--TIMI 48 trial, treatment with edoxaban 60/30 mg was superior to warfarin in the prevention of SSE and significantly reduced cardiovascular death and bleeding, especially fatal bleeding and hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

AFS Estuaries Section - A Successful Partnership

EPA Science Inventory

The Estuaries Section of the American Fisheries Society offers travel awards to students in support of their attendance and presentations at the AFS meeting. Since 2007, the Southern Association of Marine Laboratories has partnered with the Estuaries Section to sponsor two stude...

Characteristic appearances of fundus autofluorescence in treatment-naive and active polypoidal choroidal vasculopathy: a retrospective study of 170 patients.

PubMed

Zhao, Xinyu; Xia, Song; Chen, Youxin

2018-06-01

To investigate the characteristic appearances of fundus autofluorescence (FAF) in patients with treatment-naive and active polypoidal choroidal vasculopathy (PCV). Cases with the diagnosis of treatment-naive and active PCV from November 2012 to May 2017 at Peking Union Medical College Hospital were retrospectively reviewed. All patients underwent comprehensive ophthalmologic examination. Autofluorescence (AF) findings were described at the retinal sites of the corresponding lesions identified and diagnosed using indocyanine green angiography and spectral-domain optical coherence tomography. One hundred seventy patients with 192 affected eyes were included. The logMAR BCVA of the patients were 0.53 ± 0.28. The six AF patterns of 243 polypoidal lesions were confluent hypo-AF with hyper-AF ring (49.8%), confluent hypo-AF (22.6%), hyper-AF with hypo-AF ring (3.7%), granular hypo-AF (7.0%), blocked hypo-AF due to hemorrhage (8.6%), and polyps without apparent AF changes (8.2%). For 146 branching vascular networks (BVNs), 97.3% were granular hypo-AF, and others were blocked hypo-AF due to hemorrhage. In eyes with treatment-naive and active PCV, the polypoidal lesions and BVNs induce characteristic FAF changes. FAF images provide reliable adjunct reference for the diagnosis of PCV.

Quality of life and patient satisfaction in patients with atrial fibrillation on stable vitamin K antagonist treatment or switched to a non-vitamin K antagonist oral anticoagulant during a 1-year follow-up: A PREFER in AF Registry substudy.

PubMed

De Caterina, Raffaele; Brüggenjürgen, Bernd; Darius, Harald; Köhler, Sabine; Lucerna, Markus; Pecen, Ladislav; Renda, Giulia; Schilling, Richard John; Schliephacke, Tessa; Zamorano, José Luis; Le Heuzey, Jean-Yves; Kirchhof, Paulus

2018-02-01

Non-vitamin K antagonist oral anticoagulants (NOACs) are being introduced for stroke prevention in non-valvular Atrial Fibrillation (AF), and promise to be accepted better than Vitamin K Antagonists (VKAs) by patients, improving their Quality of Life (QoL). To assess to what extent patient-related factors influence decisions to switch from a VKA to a NOAC. The PREFER in AF Registry collected data at baseline in 2012 - at the beginning of NOAC prescriptions - and at 1-year follow-up, in 6412 patients in seven Western European countries. QoL and patient satisfaction questionnaires (EQ-5D-5L and/or PACT-Q2) were completed in 3777 patients at both visits. Data were compared across categories of patients on stable treatment with a VKA (i.e. continuously over the previous 12 months) (n=2102) or recently switched (within 12 months) from a VKA to a NOAC (n=213) during a 1-year follow-up, allowing a snapshot of factors influencing the switch at a time when NOACs were being introduced into the market. Compared to patients on stable treatment with a VKA, switched patients were similar in terms of age, sex, body mass index and other risk factors, but had lower prevalences of hypertension and heart valve dysfunction, and a lower rate of use of concomitant treatment with antiplatelet/anti-inflammatory agents; they also had a lower CHA 2 DS 2 -VASc score. Among 25 features investigated, switched patients more often reported bruising or bleeding, complained about bruising, were dissatisfied with the anticoagulant treatment, and reported mobility problems and anxiety/depressive traits. At the beginning of NOAC prescriptions, European doctors tended to switch from VKAs to NOACs those patients at lower risk than "non-switchers". Complaints about bruising or bleeding, dissatisfaction with treatment, mobility problems and anxiety/depression traits appear to be related to - and may have influenced - the choice to switch from a VKA to a NOAC. Copyright © 2017 Elsevier Masson SAS

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

PubMed

Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Impact of catheter ablation with remote magnetic navigation on procedural outcomes in patients with persistent and long-standing persistent atrial fibrillation.

PubMed

Jin, Qi; Pehrson, Steen; Jacobsen, Peter Karl; Chen, Xu

2015-11-01

The objectives of this study were to assess the procedural outcomes of persistent and long-standing persistent atrial fibrillation (PsAF and L-PsAF) ablation guided by remote magnetic navigation (RMN), and to detect factors predicting acute restoration of sinus rhythm (SR) by ablation with RMN. A total of 313 patients (275 male, age 59 ± 9.5 years) with PsAF (187/313) or L-PsAF (126/313) undergoing ablation using RMN were included. Patients' disease history, pulmonary venous anatomy, left atrial (LA) volume, procedure time, mapping plus ablation time, radiofrequency (RF) ablation time, fluoroscopy time, radiation dose, and complications were assessed. Stepwise regression was used to predict which variable could best predict acute restoration from AF to SR by ablation. Compared to PsAF, procedure time and RF ablation time were significantly increased in patients with L-PsAF (P = 0.01 and P < 0.001, respectively). No major complications occurred during the procedures in either PsAF or L-PsAF patients. Fifty five of 313 patients converted directly to SR by ablation. Compared to L-PsAF, the rate of SR restoration was significantly higher in PsAF (21 vs 12%, P = 0.03). Stepwise regression analysis showed LA volume was the primary parameter affecting SR restoration (P = 0.01). The LA volume of patients without direct SR restoration by ablation was 24% greater than that of patients with SR restoration (P < 0.001). Catheter ablation using RMN is a safe and effective method for PsAF and L-PsAF. LA volume could be a predictor of direct restoration of SR from sustaining AF by ablation using RMN.

Developing a New Computer-Aided Clinical Decision Support System for Prediction of Successful Postcardioversion Patients with Persistent Atrial Fibrillation.

PubMed

Sterling, Mark; Huang, David T; Ghoraani, Behnaz

2015-01-01

We propose a new algorithm to predict the outcome of direct-current electric (DCE) cardioversion for atrial fibrillation (AF) patients. AF is the most common cardiac arrhythmia and DCE cardioversion is a noninvasive treatment to end AF and return the patient to sinus rhythm (SR). Unfortunately, there is a high risk of AF recurrence in persistent AF patients; hence clinically it is important to predict the DCE outcome in order to avoid the procedure's side effects. This study develops a feature extraction and classification framework to predict AF recurrence patients from the underlying structure of atrial activity (AA). A multiresolution signal decomposition technique, based on matching pursuit (MP), was used to project the AA over a dictionary of wavelets. Seven novel features were derived from the decompositions and were employed in a quadratic discrimination analysis classification to predict the success of post-DCE cardioversion in 40 patients with persistent AF. The proposed algorithm achieved 100% sensitivity and 95% specificity, indicating that the proposed computational approach captures detailed structural information about the underlying AA and could provide reliable information for effective management of AF.

Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation.

PubMed

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2010-10-01

Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right-dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K(+) currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of I(K1) (Kir2.1 and Kir2.3) and I(K,ACh) (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) I(K,ACh) was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced I(K,ACh) in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

PubMed Central

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2018-01-01

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

Clinical and electrocardiographic characteristics for prediction of new-onset atrial fibrillation in asymptomatic patients with atrial premature complexes.

PubMed

Im, Sung Il; Park, Dong Hyun; Kim, Bong Joon; Cho, Kyoung Im; Kim, Hyun Su; Heo, Jung Ho

2018-06-01

Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. Atrial premature complexes (APCs) are commonly seen in healthy subjects. However, there was limited data about the clinical and electrocardiographic (ECG) characteristics for prediction of new-onset AF in asymptomatic patients with APCs in the long-term follow up. The Kosin University (No. 2014-02-04) 24-h holter monitoring, echocardiography, ECG database were reviewed from 2008 to 2016 to identify new- onset AF in patients with APCs. We analyzed demographic and clinical features and the nature of the APCs by ECG according to new-onset AF in those patients. Among 652 patients who underwent 24-h holter monitoring, 226 (34.4%) patients had new-onset AF. There was no difference of the baseline characteristics between new-onset AF group and non-AF group. In univariate analysis, hypertension (HTN), renal failure (CRF), high APC burdens, fastest APC running heart rate (HR), minimal HR, left ventricular ejection fraction (LVEF), left atrial volume index, peak mitral flow velocity of the early rapid filling wave and tricuspid regurgitation grade were significantly associated with new-onset AF. In multivariate analysis, higher APCs burden ( P  = 0.047), higher fastest APCs running HR ( P  = 0.034) and lower minimal HR ( P  = 0.025) were independent risk factors for new-onset AF in asymptomatic patients with APCs. Higher APCs burden, higher fastest APCs running HR and lower minimal HR were associated with new-onset AF in asymptomatic patients with APCs in the long-term follow up.

Functional characterization of the copper transcription factor AfMac1 from Aspergillus fumigatus.

PubMed

Park, Yong-Sung; Kim, Tae-Hyoung; Yun, Cheol-Won

2017-07-03

Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 ( A spergillus f umigatus Mac1 homolog) and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA-binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae , and AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1 resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1 failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of A. fumigatus failed to grow in copper-limited media, and its growth was restored by introducing ctrC We found that AfMac1 specifically bound to the promoter region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was identified from the promoter region of ctrC , and the addition of mutant ctrC lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus Furthermore, deletion of Afmac1 significantly reduced strain virulence and activated conidial killing activity by neutrophils and macrophages. Taken together, these results suggest that AfMac1 is a copper transcription factor that regulates cellular copper homeostasis in A. fumigatus . © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials.

PubMed

Reddy, Vivek Y; Doshi, Shephal K; Kar, Saibal; Gibson, Douglas N; Price, Matthew J; Huber, Kenneth; Horton, Rodney P; Buchbinder, Maurice; Neuzil, Petr; Gordon, Nicole T; Holmes, David R

2017-12-19

The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in

Simultaneous adsorption of Cu2+ and Acid fuchsin (AF) from aqueous solutions by CMC/bentonite composite.

PubMed

Gong, Ning; Liu, Yanping; Huang, Ruihua

2018-04-21

Carboxymethyl-chitosan (CMC)/bentonite composite was prepared by the method of membrane-forming, and characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) techniques. The simultaneous adsorption of Cu 2+ and Acid fuchsin (AF) applying CMC/bentonite composite as an adsorbent in single or binary systems was investigated. The adsorption study was conducted systematically by varying the ratio of CMC to bentonite, adsorbent dosage, initial pH value, initial Cu 2+ (or AF) concentration, contact time and the interaction of two components in binary solutions. The results showed that the presence of Cu 2+ hindered the adsorption of AF, while the presence of AF almost had no influence on the adsorption of Cu 2+ in binary systems. The adsorption data of Cu 2+ and AF were both suitable for Langmuir isotherm model, and the maximum adsorption capacities of CMC/bentonite composite, according to the Langmuir isotherm model were 81.4 mg/g for Cu 2+ and 253.2 mg/g for AF at 298 K. The pseudo-second-order model could better describe the adsorption process of Cu 2+ and AF. Thermodynamic constant values illustrated that the adsorption of Cu 2+ was endothermic, while the adsorption process of AF was exothermic. Copyright © 2018. Published by Elsevier B.V.

[Chronic outcome of patients with paroxysmal atrial fibrillation post catheter ablation].

PubMed

Lin, Yu-bi; Xia, Yun-long; Gao, Lian-jun; Chu, Zhen-liang; Cong, Pei-xin; Chang, Dong; Yin, Xiao-meng; Zhang, Shu-long; Yang, Dong-Hui; Yang, Yan-Zong

2009-12-01

High short-term successful rate was reported for catheter ablation in patients with paroxysmal atrial fibrillation (AF), we analyzed the long-term outcome (success rate, anticoagulation therapy and embolism event, anti-arrhythmic therapy and death post procedure) of catheter ablation for paroxysmal AF in this study. From January 2000 to December 2004, 106 consecutive patients with drug-refractory paroxysmal AF underwent catheter ablation and were followed-up for (60.7 + or - 11.8) months. Segmental pulmonary vein isolation (SPVI) was routinely performed by radiofrequency energy under the guidance of circular mapping catheter. The patients were followed up with 24 h-holter, ECG, telephone or letter. Data on recurrence of AF, the anticoagulation medication and the incidence of embolism, anti-arrhythmic therapy were obtained. There were 9 patients lost to follow up. In the remaining 97 patients [65 males, (54.8 + or - 11.2) years old], 3 cases died from cancer, sinus rhythm was maintained in 68 patients (Group S, 72.3%) and AF recurrence evidenced in 26 patients (Group R, 27.7%). In Group S, 56 patients (82.4%) discontinued anticoagulation medication, and 12 patients continued to take aspirin. There was no embolism event in Group S during follow-up. In Group R, 1 patient continued to take warfarin; 11 patients continued to take aspirin and 2 patients suffered from cerebral embolism. Anticoagulation medication was discontinued in 14 patients (53.8%) and 1 patient suffered form cerebral embolism. The incidence of embolism event in Group R is significantly higher than in Group S (P < 0.01). More patients discontinued anti-arrhythmic medication in Group S than in Group R (80.9% vs. 56.0%, P < 0.05). Catheter ablation is associated with satisfactory long-term success rate, reduced anti-arrhythmia medication, improved quality of life in patients with paroxysmal AF.

Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.

PubMed

Graves, Kevin G; May, Heidi T; Jacobs, Victoria; Bair, Tami L; Stevens, Scott M; Woller, Scott C; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Peter Weiss, J; Jared Bunch, T

2017-06-01

Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown. A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS 2 ) score calculated at the time of warfarin initiation and followed for incident dementia. The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS 2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS 2 scores strata. In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS 2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS 2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Antithrombotic treatment in elderly patients with atrial fibrillation: a practical approach.

PubMed

Suárez Fernández, Carmen; Fernández, Suárez; Formiga, Francesc; Camafort, Miguel; Cepeda Rodrigo, María; Rodrigo, Jose Cepeda; Díez-Manglano, Jesús; Pose Reino, Antonio; Reino, Pose; Tiberio, Gregorio; Mostaza, Jose María

2015-11-04

Atrial fibrillation (AF) in the elderly is a complex condition. It has a direct impact on the underuse of antithrombotic therapy reported in this population. All patients aged ≥75 years with AF have an individual yearly risk of stroke >4 %. However, the risk of hemorrhage is also increased. Moreover, in this population it is common the presence of other comorbidities, cognitive disorders, risk of falls and polymedication. This may lead to an underuse of anticoagulant therapy. Direct oral anticoagulants (DOACs) are at least as effective as conventional therapy, but with lesser risk of intracranial hemorrhage. The simplification of treatment with these drugs may be an advantage in patients with cognitive impairment. The great majority of elderly patients with AF should receive anticoagulant therapy, unless an unequivocal contraindication. DOACs may be the drugs of choice in many elderly patients with AF. In this manuscript, the available evidence about the management of anticoagulation in elderly patients with AF is reviewed. In addition, specific practical recommendations about different controversial issues (i.e. patients with anemia, thrombocytopenia, risk of gastrointestinal bleeding, renal dysfunction, cognitive impairment, risk of falls, polymedication, frailty, etc.) are provided.

Atrial fibrillation in Middle Eastern Arab and South Asian patients hospitalized with acute myocardial infarction: experience from a 20-year registry in qatar (1991-2010).

PubMed

Salam, Amar M; Al, Binali Hajar A; Singh, Rajvir; Gehani, Abdurrazzak; Asaad, Nidal; Al-Qahtani, Awad; Suwaidi, Jassim Al

2013-04-01

Recent evidence suggests that there are ethnic variations in atrial fibrillation (AF) susceptibility and incidence following acute myocardial infarction (AMI). The aim of this study was to evaluate the incidence and predictors of AF in the setting of AMI in Middle Eastern Arab and South Asian patients and its impact on in-hospital morbidity and mortality. A retrospective analysis of a prospective registry of all patients hospitalized with AMI in the state of Qatar from 1991 through 2010 was made. Clinical characteristics and outcomes of AMI patients with and without AF were compared. Sub-analysis according to ethnicity was also performed. During the 20-year period; a total of 12,881 patients were hospitalized with AMI. Of these 5028 were Arabs and 5985 were South Asians. A total of 227 had AF during hospitalization with an overall incidence of 1.8% (156 Arabs; incidence 3.1% and 48 South Asians; incidence 0.8%). The mean age of AF patients was 65 years (Arabs 69, South Asians 54). Patients with AF were significantly older and had more cardiovascular co-morbidities than patients without AF, and were more likely to have non-ST elevation AMI on presentation. Patients with AF had significantly higher in-hospital mortality rate (20.3% versus 7.1%; P=0.001) and stroke rates (1.8% versus 0.3%; P=0.001) when compared to patients without AF. Age was the only independent predictor of AF development in patients with AMI in our study. Our study reports variability in the prevalence of AF among AMI patients according to ethnicity using a 20-year registry from a Middle Eastern country. Advancing age was the major independent predictor of AF in our AMI patients. Further prospective studies are required evaluating optimal therapeutic approaches for these high-risk patients in order to reduce the high mortality observed.

Evaluation of the atoxigenic Aspergillus flavus strain AF36 in pistachio orchards

USDA-ARS?s Scientific Manuscript database

The atoxigenic strain Aspergillus flavus AF36, which has been extensively used as a biocontrol agent in commercial corn and cotton fields to reduce aflatoxin contamination, was applied in research pistachio orchards from 2002 to 2005 and in commercial pistachio orchards from 2008 to 2011. AF36 was a...

Atrial fibrillation and risk of stroke in dialysis patients

PubMed Central

Wetmore, James B.; Ellerbeck, Edward F.; Mahnken, Jonathan D.; Phadnis, Milind; Rigler, Sally K.; Mukhopadhyay, Purna; Spertus, John A.; Zhou, Xinhua; Hou, Qingjiang; Shireman, Theresa I.

2013-01-01

Purpose Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF. Methods A cohort of dually-eligible (Medicare & Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke. Results Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (HR 1.26, 99% CI’s 1.06 – 1.49, P = 0.0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African-Americans (HR 1.46, 99% CI’s 1.08 – 1.96), Hispanics (HR 1.64, 99% CI’s 1.16 – 2.31), and others (HR 1.76, 99% CI’s 1.16 – 2.78) had higher rates than did Caucasians (P < 0.001 for all). Conclusions Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes due to hemorrhage is much higher than in the general population. PMID:23332588

Atrial fibrillation and risk of stroke in dialysis patients.

PubMed

Wetmore, James B; Ellerbeck, Edward F; Mahnken, Jonathan D; Phadnis, Milind; Rigler, Sally K; Mukhopadhyay, Purna; Spertus, John A; Zhou, Xinhua; Hou, Qingjiang; Shireman, Theresa I

2013-03-01

Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF. A cohort of dually eligible (Medicare and Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke. Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (hazard ratio [HR], 1.26; 99% confidence interval [CI], 1.06-1.49; P = .0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African Americans (HR, 1.46; 99% CI, 1.08-1.96), Hispanics (HR, 1.64; 99% CI, 1.16-2.31), and others (HR, 1.76; 99% CI, 1.16-2.78) had higher rates than did Caucasians (all P < .001). Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes owing to hemorrhage is much higher than in the general population. Copyright © 2013 Elsevier Inc. All rights reserved.

External validity of the ARISTOTLE trial in real-life atrial fibrillation patients.

PubMed

Hägg, Lovisa; Johansson, Cecilia; Jansson, Jan-Håkan; Johansson, Lars

2014-10-01

Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility. We performed a cross-sectional study of an unselected population including 2274 patients in Skellefteå, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population. Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria. Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life. © 2014 John Wiley & Sons Ltd.

Patterns of Warfarin Use in Subgroups of Patients with Atrial Fibrillation: A Cross-Sectional Analysis of 430 General Practices in the United Kingdom

PubMed Central

Mohammed, Mohammed A.; Marshall, Tom; Nirantharakumar, Krishnarajah; Stevens, Andrew; Fitzmaurice, David

2013-01-01

Background Despite the proven efficacy of warfarin, its use in patients with Atrial Fibrillation (AF) is reportedly low. We investigated the underuse and overuse of warfarin in the management of AF in general practices in the United Kingdom (UK) against the National Institute of Clinical Excellence (NICE, UK) guidelines whilst seeking to identify subgroups of AF patients to inform efforts to optimise warfarin use. Methodology A retrospective database analysis to determine warfarin prescribing using tree models based on 50361 patients with AF (classified as low, moderate and high risk of stroke using CHADS2) from 430 general practices in the UK. Results Over one-third (37.0%, 4573/12351) of low risk AF patients were on warfarin, compared with 47.1% (8349/17709) moderate risk AF patients and 54.9% (11142/20301) high risk AF patients. Clinical subgroups (n = 15 low risk subgroups, n = 15 medium risk subgroups, n = 22 high risk subgroups) were identified. Several factors not supported by current guidelines (age, BMI, dementia, gender) were associated with the use of warfarin. Gender and BMI were associated with warfarin use in low and medium risk AF patients but not in high risk AF patients. Conclusion Whilst NICE guidelines suggest that all high risk AF patients should be on warfarin, half of those at moderate risk should be on warfarin and none of those at low risk should be on warfarin, we found evidence of over and under use of warfarin. Interventions to optimise warfarin therapy tailored to and targeting specific subgroups of AF patients identified by the tree models are required. PMID:23658703

Screening for Atrial Fibrillation in Patients ≥65 Years Using an Automatic Blood Pressure Monitor in a Skilled Nursing Facility.

PubMed

Wiesel, Joseph; Salomone, Thomas J

2017-10-15

Early detection of asymptomatic atrial fibrillation (AF) provides an opportunity to treat patients to reduce their risk of stroke. Long-term residents of skilled nursing facilities frequently have multiple risk factors for strokes due to AF and may benefit from screening for AF. Patients in a skilled nursing facility 65 years and older, without a history of AF and without a pacemaker or defibrillator, were evaluated using a Microlife WatchBP Home A automatic blood pressure monitor that can detect AF when set to a triple reading mode. Those with readings positive for AF were evaluated with a standard 12-lead electrocardiogram (ECG) or a 30-second single-channel ECG to confirm the presence of AF. A total of 101 patients were screened with an average age of 78 years, and 48 (48%) were female. Nine automatic blood pressure monitor readings were positive for possible AF. Of those, 7 (6.9%, 95% confidence intervals 3.0% to 14.2%) had AF confirmed with ECG. Only 2 (2%, 95% confidence interval 0.3% to 7.7%) were false-positive readings. One-time screening for AF using an automatic blood pressure monitor in a skilled nursing facility resulted in a high number of patients with newly diagnosed AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Myocardial architecture and patient variability in clinical patterns of atrial fibrillation

NASA Astrophysics Data System (ADS)

Manani, Kishan A.; Christensen, Kim; Peters, Nicholas S.

2016-10-01

Atrial fibrillation (AF) increases the risk of stroke by a factor of 4-5 and is the most common abnormal heart rhythm. The progression of AF with age, from short self-terminating episodes to persistence, varies between individuals and is poorly understood. An inability to understand and predict variation in AF progression has resulted in less patient-specific therapy. Likewise, it has been a challenge to relate the microstructural features of heart muscle tissue (myocardial architecture) with the emergent temporal clinical patterns of AF. We use a simple model of activation wave-front propagation on an anisotropic structure, mimicking heart muscle tissue, to show how variation in AF behavior arises naturally from microstructural differences between individuals. We show that the stochastic nature of progressive transversal uncoupling of muscle strands (e.g., due to fibrosis or gap junctional remodeling), as occurs with age, results in variability in AF episode onset time, frequency, duration, burden, and progression between individuals. This is consistent with clinical observations. The uncoupling of muscle strands can cause critical architectural patterns in the myocardium. These critical patterns anchor microreentrant wave fronts and thereby trigger AF. It is the number of local critical patterns of uncoupling as opposed to global uncoupling that determines AF progression. This insight may eventually lead to patient-specific therapy when it becomes possible to observe the cellular structure of a patient's heart.

Damage to cochlear efferents following AF64A intoxication.

PubMed

Smith, D W; Mount, R J

1993-07-01

Damage to cochlear efferents in chinchillas was assessed using transmission electron microscopy following unilateral treatment with the cholinotoxin ethylcholine mustard aziridinium ion (AF64A). AF64A was diluted in artificial perilymph to concentrations ranging from 0.5 to 100 microM. Survival times ranged from 1 to 12 weeks. At concentrations above 10 microM, widespread damage was noted to efferent fibers within the inner spiral bundle (ISB), tunnel spiral bundle (TSB), tunnel radial fibers (TRF) and efferent terminals at the base of OHCs. This damage included degeneration of fibers and terminals, delamination of mitochondria, vacuolization, and loss of cell membrane. However, at high concentrations, non-specific damage was also noted as thinnings or discontinuities of the membrane of OHCs and afferent fibers. At concentrations between 3 and 10 microM, selective damage was observed to efferent fibers within the ISB, TSB, TRF, and to terminals at the base of the OHCs, with all other structures appearing normal. At concentrations of 0.5 and 1 microM, damage was limited to efferent fibers within the TSB and ISB below the inner hair cells. In general, insult was greatest to middle- and basal-turn efferents, and longer survival times did not produce greater damage to, or loss of, efferents. These data suggest that at low concentrations, AF64A produces a partial yet selective degeneration of cochlear efferents within both the medial and lateral tracts, and that at the lowest concentrations used in these studies, AF64A produces a preferential insult on lateral olivocochlear efferents.

The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jeonghee; Chung, In Kwon, E-mail: topoviro@yonsei.ac.kr

Highlights: •Identification of U2AF65 as a novel TRF1-interacting protein. •U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. •U2AF65 interferes with the interaction between TRF1 and Fbx4. •U2AF65 represents a new route for modulating TRF1 function at telomeres. -- Abstract: The human telomeric protein TRF1 is a component of the six-subunit protein complex shelterin, which provides telomere protection by organizing the telomere into a high-order structure. TRF1 functions as a negative regulator of telomere length by controlling the access of telomerase to telomeres. Thus, the cellular abundance of TRF1 at telomeres should be maintained and tightly regulated to ensure propermore » telomere function. Here, we identify U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 (U2AF65), an essential pre-mRNA splicing factor, as a novel TRF1-interacting protein. U2AF65 interacts with TRF1 in vitro and in vivo and is capable of stabilizing TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. We also found that U2AF65 interferes with the interaction between TRF1 and Fbx4, an E3 ubiquitin ligase for TRF1. Depletion of endogenous U2AF65 expression by short interfering RNA (siRNA) reduced the stability of endogenous TRF1 whereas overexpression of U2AF65 significantly extended the half-life of TRF1. These findings demonstrate that U2AF65 plays a critical role in regulating the level of TRF1 through physical interaction and ubiquitin-mediated proteolysis. Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres.« less

Family history of atrial fibrillation as a predictor of atrial substrate and arrhythmia recurrence in patients undergoing atrial fibrillation catheter ablation.

PubMed

Kapur, Sunil; Kumar, Saurabh; John, Roy M; Stevenson, William G; Tedrow, Usha B; Koplan, Bruce A; Epstein, Laurence M; MacRae, Calum A; Michaud, Gregory F

2018-06-01

A commonly held notion is that patients with a family history of atrial fibrillation (AF) have worse atrial substrate and higher rates of arrhythmia recurrence following ablation. We sought to examine differences in atrial substrate and catheter ablation outcomes in patients with a 1st degree family member with paroxysmal or persistent AF (PeAF) compared to those without. A total of 256 consecutive patients undergoing their 1st ablation for AF (123 paroxysmal, 133 persistent) with >1 year follow up were included. The presence of one 1st-degree family relative was defined as a 'positive family history'. Clinical characteristics, electroanatomic map findings, ablation characteristics and outcomes were compared in patients with and without a positive family history of AF. Patients with paroxysmal fibrillation with a positive family history (n = 57; 46%) had similar clinical characteristics and arrhythmia recurrence after catheter ablation as those without. Of those that recurred, patients with a positive family history were more likely to have progressed to PeAF (P = 0.05). Patients with PeAF with a positive family history (n = 75; 56%) had similar clinical characteristics, electroanatomic mapping findings and ablation characteristics, but worse long term arrhythmia free survival (P = 0.04). The presence of a 1st-degree family member with AF does not impact the clinical outcomes of catheter ablation for paroxysmal AF. However, a positive family history is associated with worse arrhythmia free survival in patients with PeAF. This finding is not explained by differences in clinical characteristics, atrial substrate assessed by voltage maps or ablation characteristics.

Neglecting Democracy in Education Policy: A-F School Report Card Accountability Systems

ERIC Educational Resources Information Center

Murray, Kevin; Howe, Kenneth R.

2017-01-01

Sixteen states have adopted school report card accountability systems that assign A-F letter grades to schools. Other states are now engaged in deliberation about whether they, too, should adopt such systems. This paper examines A-F accountability systems with respect to three kinds of validity. First, it examines whether or not these…

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

PubMed

Molnar, Amber O; Eddeen, Anan Bader; Ducharme, Robin; Garg, Amit X; Harel, Ziv; McCallum, Megan K; Perl, Jeffrey; Wald, Ron; Zimmerman, Deborah; Sood, Manish M

2017-07-06

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

New Oral Anticoagulants May Be Particularly Useful for Asian Stroke Patients

PubMed Central

Bang, Oh Young; Hong, Keun-Sik; Heo, Ji Hoe; Koo, Jaseong; Kwon, Sun U.; Yu, Kyung-Ho; Bae, Hee-Joon; Lee, Byung-Chul; Yoon, Byung-Woo

2014-01-01

Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in

[Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

PubMed

Xu, Si-Miao; Yang, Yang; Zhou, Mi; Zhao, Xue-Jiao; Qin, Yu; Zhang, Pei-Ling; Yuan, Rui-Feng; Zhou, Jian-Feng; Fang, Yong

2013-10-01

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

Factors associated with the development of atrial fibrillation in patients with rheumatic mitral stenosis.

PubMed

Ozaydin, Mehmet; Turker, Yasin; Varol, Ercan; Alaca, Sule; Erdogan, Dogan; Yilmaz, Nigar; Dogan, Abdullah

2010-06-01

The aim of this study was to evaluate the factors associated with the development of atrial fibrillation (AF) in patients with rheumatic mitral stenosis (MS). A total of 146 consecutive patients with rheumatic MS were screened. They were accepted to be in AF group and sinus rhythm group according to their rhythm in the baseline ECG. After screening, 38 patients were excluded due to hyperthyroidism (n = 13), chronic obstructive pulmonary disease (n = 22), malignancy (n = 2) and rheumatoid arthritis (n = 1). Therefore, remaining 108 patients, 74 of whom in sinus rhythm (MS-SR) and 34 of whom in AF (MS-AF) constituted study population. Fourty age- and gender-matched patients constituted control group. Factors associated with development of AF in multivariable analysis included High sensitivity C reactive protein (P = 0.005; odds ratio, 3.44; 95% confidence interval, 1.44-8.22), N-terminal of brain natriuretic peptide precursor (P < 0.0001; odds ratio, 1.03; 95% confidence interval, 1.02-1.06) and left atrial diameter (P < 0.0001; odds ratio, 1.68; 95% confidence interval, 1.32-2.14). Present study suggests that High sensitivity C reactive protein, N-terminal of brain natriuretic peptide precursor and left atrial diameter are associated with development AF in patients with MS.

Pathway and rate-limiting step of glyphosate degradation by Aspergillus oryzae A-F02.

PubMed

Fu, Gui-Ming; Chen, Yan; Li, Ru-Yi; Yuan, Xiao-Qiang; Liu, Cheng-Mei; Li, Bin; Wan, Yin

2017-09-14

Aspergillus oryzae A-F02, a glyphosate-degrading fungus, was isolated from an aeration tank in a pesticide factory. The pathway and rate-limiting step of glyphosate (GP) degradation were investigated through metabolite analysis. GP, aminomethylphosphonic acid (AMPA), and methylamine were detected in the fermentation liquid of A. oryzae A-F02, whereas sarcosine and glycine were not. The pathway of GP degradation in A. oryzae A-F02 was revealed: GP was first degraded into AMPA, which was then degraded into methylamine. Finally, methylamine was further degraded into other products. Investigating the effects of the exogenous addition of substrates and metabolites showed that the degradation of GP to AMPA is the rate-limiting step of GP degradation by A. oryzae A-F02. In addition, the accumulation of AMPA and methylamine did not cause feedback inhibition in GP degradation. Results showed that degrading GP to AMPA was a crucial step in the degradation of GP, which determines the degradation rate of GP by A. oryzae A-F02.

Low strain, long life creep fatigue of AF2-1DA and INCO 718

NASA Technical Reports Server (NTRS)

Thakker, A. B.; Cowles, B. A.

1983-01-01

Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

[Electrophysiological findings and ablation strategies in patients with atrial tachyarrhythmias after left atrial circumferential ablation in the treatment of atrial fibrillation].

PubMed

Chen, Ming-long; Yang, Bing; Xu, Dong-jie; Zou, Jian-gang; Shan, Qi-jun; Chen, Chun; Chen, Hong-wu; Li, Wen-qi; Cao, Ke-jiang

2007-02-01

To report the electrophysiological findings and the ablation strategies in patients with atrial tachyarrhythmias (ATAs) or atrial fibrillation (AF) recurrence after left atrial circumferential ablation (LACA) in the treatment of AF. 91 patients with AF had LACA procedure from April 2004 to May 2006, 19 of which accepted the second ablation procedure due to ATAs or AF recurrence. In all the 19 patients [17 male, 2 female, age 25 - 65 (53 +/- 12) years], 11 presented with paroxysmal AF before the first ablation procedure, 2 with persistent AF and 6 with permanent AF. Pulmonary vein potentials (PVP) were investigated in both sides in all the patients. Delayed PVP was identified inside the left circular line in 5 patients, in the right in 1 and both in 2 during sinus rhythm. "Gap" conduction was found and successfully closed guided by circular mapping catheter. In 3 cases, irregular left atrial tachycardia was caused by fibrillation rhythm inside the left ring via decremental "gap" conduction. Reisolation was done successfully again guided by 3-D mapping and made the left atrium in sinus rhythm but the fibrillation rhythm was still inside the left ring. Pulmonary vein tachycardia with 1:1 conduction to the left atrium presented in one case and reisolation stopped the tachycardia. No PVP was discovered in both sides in 4 patients but other tachycardias could be induced, including two right atrial scar related tachycardias, two supraventricular tachycardias mediated by concealed accessory pathway, one cavo-tricuspid isthmus dependent atrial flutter and one focal atrial tachycardia near the coronary sinus ostium. All the tachycardias in these 4 patients were successfully ablated with the help of routine and 3-D mapping techniques. In the rest 3, which were in AF rhythm, LACA was successfully done again. After a mean follow-up of 4 - 26 (11.5 +/- 8.5) months, 16 patients were symptom free without anti-arrhythmic drug therapy; 1 of them had frequent palpitation attack with

Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation.

PubMed

Tanigawa, Takahiko; Kaneko, Masato; Hashizume, Kensei; Kajikawa, Mariko; Ueda, Hitoshi; Tajiri, Masahiro; Paolini, John F; Mueck, Wolfgang

2013-01-01

The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.

Brain and kidney, victims of atrial microembolism in elderly hospitalized patients? Data from the REPOSI study.

PubMed

Corrao, S; Argano, C; Nobili, A; Marcucci, M; Djade, C D; Tettamanti, M; Pasina, L; Franchi, C; Marengoni, A; Salerno, F; Violi, F; Mannucci, P M; Perticone, F

2015-05-01

It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

EWOLUTION: Design of a registry to evaluate real-world clinical outcomes in patients with AF and high stroke risk-treated with the WATCHMAN left atrial appendage closure technology.

PubMed

Boersma, Lucas V A; Schmidt, Boris; Betts, Tim R; Sievert, Horst; Tamburino, Corrado; Teiger, Emmanuel; Stein, Kenneth M; Bergmann, Martin W

2016-09-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the rate of ischemic stroke attributed to non-valvular AF is estimated at 5% per year. Several multi-center studies established left atrial appendage closure as a safe and effective alternative to oral anticoagulation, but there is a need for additional real world data. The purpose of this observational, prospective, single-arm, multicenter clinical study is to compile real-world clinical outcome data for WATCHMAN™ LAA (left atrial appendage) Closure Technology. One thousand subjects at up to 70 institutions in Europe, the Middle East, and Russia will be enrolled. Patients will be followed for 2 years after WATCHMAN implantation, according to standard medical practice. Primary endpoints include procedural and long-term data including stroke/embolism, bleeding, and death. This article presents the background of the LAAC device and describes the design of the study. Results for peri-procedural analyses are expected toward the end of 2015; long-term follow-up data are expected in the latter half of 2017. The EWOLUTION study will formally expand knowledge of LAA closure into a broader real world setting. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Clinical significance of nutritional status in patients with atrial fibrillation: An overview of current evidence.

PubMed

Anaszewicz, Marzena; Budzyński, Jacek

2017-05-01

Obesity is a well-known atherosclerosis risk factor; however, its role and the importance of undernutrition in atrial fibrillation (AF) pathogenesis are still not well understood. The aim of this study was to present the current state of knowledge on this issue in different groups of patients. Systematic review of papers published between 1980 and 2016. The literature shows contradicting views regarding the impact of nutritional status on the risk, course, and complications of AF. On the one hand, it has been revealed that overweight, obesity, and high birth mass increase the risk of AF, and that their reduction is linked to an improved course of AF and reduced all-cause and cardiovascular mortality. On the other hand, a so-called obesity paradox has been found, which shows lower all-cause mortality in overweight patients with AF compared to those of normal weight or who are underweight. It has also been shown, although based on a small number of studies, that the relationship between nutritional status and risk of AF and its complication may be U-shaped, which means that not only patients with obesity, but also individuals with underweight, cachexia, and low birth weight may have an increased risk and poor outcome of AF. The relationship between patients' nutritional status and the course of AF has become clearer but it requires further studies examining the importance of weight reduction on AF course. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Renal denervation for improving outcomes of catheter ablation in patients with atrial fibrillation and hypertension: early experience.

PubMed

Pokushalov, Evgeny; Romanov, Alexander; Katritsis, Demosthenes G; Artyomenko, Sergey; Bayramova, Sevda; Losik, Denis; Baranova, Vera; Karaskov, Alexander; Steinberg, Jonathan S

2014-07-01

The potential role of renal denervation (RD) in patients with AF and less severe hypertension is unknown. The purpose of this study was to assess the potential role of RD as an adjunct to pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) and moderate resistant or severe resistant hypertension. The data for this study were obtained from 2 different prospective randomized studies, analyzed by meta-analysis. Patients with paroxysmal AF or persistent AF and moderate resistant hypertension (office blood pressure BP ≥140/90 mm Hg and <160/100 mm Hg; first study; n = 48) or severe resistant hypertension (≥160/100 mm Hg; second study; n = 38) were randomized to PVI or PVI with RD. At 12 months, 26 of the 41 PVI with RD patients (63%) were AF-free vs 16 of the 39 patients (41%) in the PVI-only group (P = .014). In patients with severe hypertension, 11 of the 18 PVI with RD patients (61%) vs 5 of the 18 PVI-only patients (28%) were AF-free (P = .03). For moderate hypertension, the differences were less dramatic: 11 of 21 (52%) vs 15 of 23 (65%) when RD added (P = .19). The superior efficacy of adding RD was most apparent in persistent AF and severe hypertension (hazard ratio 0.25, confidence interval 0.09-0.72, P = .01). Duration of the procedure and fluoroscopy were nonsignificantly longer in the RD group. RD may improve the results of PVI in patients with persistent AF and/or severe resistant hypertension. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation.

PubMed

Kawabata, Mihoko; Goya, Masahiko; Takagi, Takamitsu; Yamashita, Shu; Iwai, Shinsuke; Suzuki, Masahito; Takamiya, Tomomasa; Nakamura, Tomofumi; Hayashi, Tatsuya; Yagishita, Atsuhiko; Sasaki, Takeshi; Takahashi, Yoshihide; Ono, Yuhichi; Hachiya, Hitoshi; Yamauchi, Yasuteru; Otomo, Kenichiro; Nitta, Junichi; Okishige, Kaoru; Nishizaki, Mitsuhiro; Iesaka, Yoshito; Isobe, Mitsuaki; Hirao, Kenzo

2016-12-01

Atrial fibrillation (AF) often coexists with Wolff-Parkinson-White (WPW) syndrome. We compared the efficacy of Kent bundle ablation alone and additional AF ablation on accompanying AF, and examined which patients would still have a risk of AF after successful Kent bundle ablation. This retrospective multicenter study included 96 patients (56±15 years, 72 male) with WPW syndrome and AF undergoing Kent bundle ablation. Some patients underwent simultaneous pulmonary vein isolation (PVI) for AF. The incidence of post-procedural AF was examined. Sixty-four patients underwent only Kent bundle ablation (Kent-only group) and 32 also underwent PVI (+PVI group). There was no significant difference in the basic patient characteristics between the groups. Additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p=0.53). In the Kent-only group, AF episodes remained in 25.0% during the follow-up (709 days). A univariate analysis showed that age ≥60 years, left atrial dimension ≥38mm, B-type natriuretic peptide (BNP) ≥40pg/ml, and concomitant hypertension were predictive factors for residual AF. However, in the multivariate analysis, only BNP ≥40pg/ml remained as an independent predictive factor (HR=17.1 and CI: 2.3-128.2; p=0.006). Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact of preventing recurrence of AF in select patients. Screening the BNP level would help decide the strategy to manage those patients. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Left atrial appendage obliteration in atrial fibrillation patients undergoing bioprosthetic mitral valve replacement.

PubMed

Min, X P; Zhu, T Y; Han, J; Li, Y; Meng, X

2016-02-01

Left atrial appendage (LAA) obliteration is a proven stroke-preventive measure for patients with nonvalvular atrial fibrillation (AF). However, the efficacy of LAA obliteration for patients with AF after bioprosthetic mitral valve replacement (MVR) remains unclear. This study aimed to estimate the efficacy of LAA obliteration in preventing embolism and to investigate the predictors of thromboembolism after bioprosthetic MVR. We retrospectively studied 173 AF subjects with bioprosthetic MVR; among them, 81 subjects underwent LAA obliteration using an endocardial running suture method. The main outcome measure was the occurrence of thrombosis events (TEs). The mean follow-up time was 40 ± 17 months. AF rhythm was observed in 136 patients postoperatively. The incidence rate of TEs was 13.97 % for postoperative AF subjects; a dilated left atrium (LA; > 49.5 mm) was identified as an independent risk factor of TEs (OR = 10.619, 95 % CI = 2.754-40.94, p = 0.001). For postoperative AF patients with or without LAA, the incidence rate of TEs was 15.8 % (9/57) and 12.7 % (10/79; p = 0.603), respectively. The incidence rate of TEs was 2.7 % (1/36) and 4.2 % (2/48) for the subgroup patients with a left atrial diameter of < 49.5 mm, and 38.1 % (8/21) and 25.8 % (8/31) for those with a left atrial diameter of > 49.5 mm (p = 0.346). Surgical LAA obliteration in patients with valvular AF undergoing bioprosthetic MVR did not reduce TEs, even when the CHA2DS2-VASc score (a score for estimating the risk of stroke in AF) was ≥ 2 points.

Sentence processing and verbal working memory in a white-matter-disconnection patient.

PubMed

Meyer, Lars; Cunitz, Katrin; Obleser, Jonas; Friederici, Angela D

2014-08-01

The Arcuate Fasciculus/Superior Longitudinal Fasciculus (AF/SLF) is the white-matter bundle that connects posterior superior temporal and inferior frontal cortex. Its causal functional role in sentence processing and verbal working memory is currently under debate. While impairments of sentence processing and verbal working memory often co-occur in patients suffering from AF/SLF damage, it is unclear whether these impairments result from shared white-matter damage to the verbal-working-memory network. The present study sought to specify the behavioral consequences of focal AF/SLF damage for sentence processing and verbal working memory, which were assessed in a single patient suffering from a cleft-like lesion spanning the deep left superior temporal gyrus, sparing most surrounding gray matter. While tractography suggests that the ventral fronto-temporal white-matter bundle is intact in this patient, the AF/SLF was not visible to tractography. In line with the hypothesis that the AF/SLF is causally involved in sentence processing, the patient׳s performance was selectively impaired on sentences that jointly involve both complex word orders and long word-storage intervals. However, the patient was unimpaired on sentences that only involved long word-storage intervals without involving complex word orders. On the contrary, the patient performed generally worse than a control group across standard verbal-working-memory tests. We conclude that the AF/SLF not only plays a causal role in sentence processing, linking regions of the left dorsal inferior frontal gyrus to the temporo-parietal region, but moreover plays a crucial role in verbal working memory, linking regions of the left ventral inferior frontal gyrus to the left temporo-parietal region. Together, the specific sentence-processing impairment and the more general verbal-working-memory impairment may imply that the AF/SLF subserves both sentence processing and verbal working memory, possibly pointing to the AF

Treatment Guidelines of Atrial Fibrillation (AFib or AF)

MedlinePlus

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Treatment Guidelines of Atrial Fibrillation (AFib or AF) Updated:Jun 28,2017 What are the treatment guidelines for atrial fibrillation? Medical guidelines are written by ...

AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

PubMed Central

Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

2016-01-01

The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation.

PubMed

Zhao, Fei; Zhang, Shijiang; Shao, Yongfeng; Wu, Yanhu; Qin, Jianwei; Chen, Yijiang; Chen, Liang; Gu, Haitao; Wang, Xiaowei; Huang, Chenjun; Zhang, Wei

2013-10-03

The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5. Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prevalence of conduction delay of the right atrium in patients with SSS: implications for pacing site selection.

PubMed

Verlato, Roberto; Zanon, Francesco; Bertaglia, Emanuele; Turrini, Pietro; Baccillieri, Maria Stella; Baracca, Enrico; Bongiorni, Maria Grazia; Zampiero, Aldo; Zonzin, Pietro; Pascotto, Pietro; Venturini, Diego; Corbucci, Giorgio

2007-09-01

To evaluate the prevalence of severe right atrial conduction delay in patients with sinus node dysfunction (SND) and atrial fibrillation (AF) and the effects of pacing in the right atrial appendage (RAA) and in the inter-atrial septum (IAS). Forty-two patients (15 male, 72 +/- 7 years) underwent electrophysiologic study to measure the difference between the conduction time from RAA to coronary sinus ostium during stimulation at 600 ms and after extrastimulus (DeltaCTos). Patients were classified as group A if DeltaCTos > 60 ms and group B if < 60 ms. Each Group was randomized to RAA/IAS pacing and algorithms ON/OFF. Fifteen patients (36%, group A) had DeltaCTos = 76 +/- 11 ms and 27 patients (64%, group B) had DeltaCTos = 36 +/- 20 ms. Twenty-two patients were paced at the RAA and 20 at the IAS. During the study, no AF recurrences were reported in 11 of 42 (26%) patients, independently of RAA or IAS pacing. Patients from group A and RAA pacing had 0.79 +/- 0.81 episodes of AF/day during DDD, which increased to 1.52 +/- 1.41 episodes of AF/day during DDDR + Alg (P = 0.046). Those with IAS pacing had 0.5 +/- 0.24 episodes of AF/day during DDD, which decreased to 0.06 +/- 0.08 episodes of AF/day during DDDR + Alg (P = 0.06). In group B, no differences were reported between pacing sites and pacing modes. Severe right atrial conduction delay is present in one-third of patients with SND and AF: continuous pacing at the IAS is superior to RAA for AF recurrences. In patients without severe conduction delay, no differences between pacing site or mode were observed.

Health Literacy and Atrial Fibrillation: Relevance and Future Directions for Patient-centred Care.

PubMed

Aronis, Konstantinos N; Edgar, Brittany; Lin, Wendy; Martins, Maria Auxiliadora Parreiras; Paasche-Orlow, Michael K; Magnani, Jared W

2017-01-01

Atrial fibrillation (AF) is a common cardiac arrhythmia with significant clinical outcomes, and is associated with high medical and social costs. AF is complicated for patients because of its specialised terminology, long-term adherence, symptom monitoring, referral to specialty care, array of potential interventions and potential for adversity. Health literacy is a frequently under-recognised, yet fundamental, component towards successful care in AF. Health literacy is defined as the capacity to obtain, process and understand health information, and has had markedly limited study in AF. However, health literacy could contribute to how patients interpret symptoms, navigate care, and participate in treatment evaluation and decision-making. This review aims to summarise the clinical importance and essential relevance of health literacy in AF. We focus here on central aspects of AF care that are most related to self-care, including understanding the symptoms of AF, shared decision-making, adherence and anticoagulation for stroke prevention. We discuss opportunities to enhance AF care based on findings from the literature on health literacy, and identify important gaps. Our overall objective is to articulate the importance and relevance of integrating health literacy in the care of individuals with AF.

Can thromboembolic risk be associated with erectile dysfunction in atrial fibrillation patients?

PubMed

Szymański, Filip M; Filipiak, Krzysztof J; Płatek, Anna E; Kotkowski, Marcin; Opolski, Grzegorz

2015-01-01

Erectile dysfunction (ED) is highly prevalent in patients with diseases of cardiovascular system, including patients with atrial fibrillation (AF). Reasons for this high co-prevalence include endothelial dysfunction, inflammation, oxidative and emotional stress associated with AF. Association of AF-induced prothrombotic state and possible microthrombi in penile arteries with ED remains unclear. The present study aims to assess if probability of AF-associated risk of peripheral thromboembolism may be associated with ED in AF patients. Probability of thromboembolic complications was assessed with two commonly used risk scores CHADS₂ and CHA2DS₂-VASc in a group of continuous AF patients. All patients were also asked to fill an IIEF-5 questionnaire designed for screening for ED. Mean CHADS₂ score in the whole study group was 1.1 ± 1.0 points and CHA₂DS₂- -VASc was 1.5 ± 1.4 points. ED was present in 57.4% of the 129-person study population. In patients with ED, both CHADS₂ (0.9 ± 1.0 vs. 1.3 ± 1.1; p = 0.03) and CHA₂DS₂-VASc (1.2 ± 1.1 vs. 1.8 ± 1.5; p = 0.03) scores were significantly higher than in the group without dysfunction. After dividing the patients according to age into groups younger than 65 years vs. ≥ 65 years, observed correlation was no longer significant in the younger group (p > 0.05). In patients ≥ 65 years, in whom the risk scores are routinely used, dysfunction both CHADS₂ (1.1 ± 0.9 vs. 2.0 ± 0.9; p = 0.02) and CHA₂DS₂-VASc (2.3 ± 1.1 vs. 3.4 ± 1.3; p = 0.04) scores were higher in the group with ED. Erectile dysfunctions in AF patients are associated with elevated cardioembolic risk. We postulate that the diagnosis of ED should be considered an additional marker of prothrombotic state, and may be useful in clinical decision-making, especially in patients ≥ 65 years old.

A Specific Antibody to Neuropeptide AF1 (KNEFIRFamide) Recognizes a Small Subset of Neurons in Ascaris suum: Differences from Caenorhabditis elegans

PubMed Central

Sithigorngul, Paisarn; Jarecki, Jessica L.; Stretton, Antony O.W.

2016-01-01

A monoclonal antibody, AF1-003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C-terminal FIR-Famide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide-like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two-step HPLC, the only fractions recognized by AF1-003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1-003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or -B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp-8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540– 550); the URX neurons express AF1 in both species, but, in C. elegans, flp-8 expression was not detected in RIP, PQR, and PDA or -B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. PMID:21452223

An Evaluation of the Impacts of AF-M315E Propulsion Systems for Varied Mission Applications

NASA Technical Reports Server (NTRS)

Deans, Matthew C.; Oleson, Steven R.; Fittje, James; Colozza, Anthony; Packard, Tom; Gyekenyesi, John; McLean, Christopher H.; Spores, Ronald A.

2015-01-01

The purpose of the AF-M315E COMPASS study is to identify near-term (3-5 years) and long term (5 years +) opportunities for infusion, specifically the thruster and associated component technologies being developed as part of the GPIM project. Develop design reference missions which show the advantages of the AF-M315E green propulsion system. Utilize a combination of past COMPASS designs and selected new designs to demonstrate AF-M315E advantages. Use the COMPASS process to show the puts and takes of using AF-M315E at the integrated system level.

Effects of repeated administration of (-)-nicotine on AF64A-induced learning and memory impairment in rats.

PubMed

Hiramatsu, M; Yamatsu, T; Kameyama, T; Nabeshima, T

2002-03-01

It has been reported that pretreatment with (-)-nicotine prevents glutamate- and amyloid beta protein (Abeta)-induced cytotoxicity in vitro. However, few studies on the neuroprotective effects of (-)-nicotine in vivo have been reported. We examined whether repeated administration of (-)-nicotine exhibits neuroprotective effects in AF64A-treated rats. (-)-Nicotine (0.1 and 0.2 mg/kg, s.c.) was administered once a day for 28 days. On day 14, AF64A (2.5 nmol/side) was injected bilaterally into the hippocampus. Intrahippocampal injection of AF64A showed severe impairment of learning and memory in rats in the water maze and passive avoidance tests. Repeated administration of (-)-nicotine (0.1 and 0.2 mg/kg, s.c.) did not reverse the impairment of memory induced by AF64A in the water maze test. Interestingly, the (-)-nicotine (0.1 and 0.2 mg/kg, s.c.)-treated group showed weak impairment of learning and memory after AF64A treatment compared to the (AF64A + saline)-treated group in the passive avoidance test. These results suggested that (-)-nicotine may have neuroprotective effects against the neurotoxicity induced by AF64A.

Atrial fibrillation in patients on haemodialysis in Andalusia. Prevalence, clinical profile and therapeutic management.

PubMed

Sánchez Perales, Carmen; Vázquez Sánchez, Teresa; Salas Bravo, Daniel; Ortega Anguiano, Sonia; Vázquez Ruiz de Castroviejo, Eduardo

Atrial fibrillation (AF) represents an important social and healthcare problem. There is wide variability in the prevalence of this arrhythmia in studies analysing patients on haemodialysis (HD). To investigate the prevalence, clinical profile and therapeutic management of patients with AF on HD in Andalusia. We asked the public healthcare system of Andalusia to provide us with the number of patients who were being treated with HD. We asked attending nephrologists from all hospital and outpatient centres in 5 of the 8 Andalusian provinces to perform an electrocardiogram and to fill out a questionnaire on patients selected by simple random sampling. A total of 2,348 patients were being treated with HD in the 5provinces included in the study. The estimated sample size was 285 patients. We obtained an electrocardiogram and information from 252 patients (88.4%); mean age 65.3±16 years; 40.9% women. Sixty-three patients (25%) had AF. Of these, 36 (14.3%) had AF in the recorded ECG and in the rest it had been documented previously. In the multivariate analysis, older age (OR: 1.071; 95% CI: 1.036-1.107; P=0.000) and greater time on HD (OR: 1.009; 95% CI: 1.004-1.014; P=0.000) were independently associated with the presence of AF. Of the patients with AF, 41.3% were on anticoagulant treatment at the time of the study; and 41.2% were on antiplatelet agents. AF in dialysis units is an important finding. Establishing the risk-benefit ratio of anticoagulant treatment constitutes a real challenge. Well-designed clinical trials are pivotal in order to define the rational use of antithrombotic drugs. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

The influence of depression and anxiety symptoms on health-related quality of life in patients with atrial fibrillation and atrial flutter.

PubMed

Akintade, Bimbola Fola; Chapa, Deborah; Friedmann, Erika; Thomas, Sue Ann

2015-01-01

The health-related quality of life (HRQoL) of patients with atrial fibrillation (AF) and atrial flutter (AFL) is an important issue in cardiovascular health management. Determinants of poor HRQoL of AF/AFL patients require further elucidation. The purpose of this study was to evaluate the influencing factors related to the HRQoL of AF/AFL patients. In 150 consecutively recruited patients in a multicenter, cross-sectional study from April 2010 to February 2011, depression and anxiety were measured with the Beck Depression Inventory II and the State Trait Anxiety Inventory, respectively, whereas HRQoL was assessed with the generic Medical Outcomes Survey 36-Item Short-Form Survey version 2 and the Symptom Checklist. Linear regression modeling was performed to determine predictors of HRQoL among variables, including the patients' age, gender, race, marital status, type of AF/AFL, frequency of AF/AFL symptoms, time since diagnosis, and anxiety and depression symptoms. Female patients with AF/AFL reported poorer physical HRQoL than male patients did (P < .001, R² = 0.391). Symptoms of depression and anxiety were found to be associated with poorer HRQoL (P < .001, R² = 0.482). Anxiety was the strongest predictor of the mental component of the Medical Outcomes Survey 36-Item Short-Form Survey version 2 and the Symptom Checklist. Younger patients had worse AF/AFL-related symptoms and severity than older patients did (P < .001, R² = 0.302). Increased frequency of symptomatic episodes was associated with worse AF/AFL-related symptoms and severity. In conclusion, depression and anxiety symptoms and female gender emerged as clear indicators of poor HRQoL in AF/AFL patients. These risk factors should be used to identify patients who may require additional evaluation and treatment efforts to manage their cardiac conditions or HRQoL. Interventions to improve HRQoL in these individuals require further investigation.

Diffusion Tensor Imaging Studies on Arcuate Fasciculus in Stroke Patients: A Review

PubMed Central

Jang, Sung Ho

2013-01-01

Aphasia is one of the most common and devastating sequelae of stroke. The arcuate fasciculus (AF), an important neural tract for language function, connects Broca’s and Wernicke’s areas. In this review article, previous diffusion tensor imaging (DTI) studies on the AF in stroke patients were reviewed with regard to the usefulness for diagnosis (seven studies), prediction of prognosis (two studies), and recovery of aphasia (three studies). Although scant studies on this topic have been conducted in stroke patients, DTI for the AF appears to provide useful information on the presence or severity of injury of the AF, prognosis prediction of aphasia, and recovery mechanisms of aphasia in stroke patients. Therefore, further DTI studies on these topics should be encouraged, especially studies on prognosis prediction and recovery mechanisms of aphasia. In addition, research on other neural tracts known to be involved in aphasia as well as the AF in both hemispheres should be encouraged. PMID:24198780

Fragmented QRS may predict new onset atrial fibrillation in patients with ST-segment elevation myocardial infarction.

PubMed

Yesin, Mahmut; Kalçık, Macit; Çağdaş, Metin; Karabağ, Yavuz; Rencüzoğulları, İbrahim; Gürsoy, Mustafa Ozan; Efe, Süleyman Çağan; Karakoyun, Süleyman

Fragmented QRS (fQRS) has been shown to be a marker of local myocardial conduction abnormalities, cardiac fibrosis in previous studies. It was also reported to be a predictor of sudden cardiac death and increased morbidity and mortality in selected populations. However, there is no study investigating the role of fQRS in the development of atrial fibrillation in patients with ST segment elevation myocardial infarction (STEMI). In this study we aimed to investigate the relationship between the presence of fQRS after primary percutaneous coronary intervention (pPCI) and in-hospital development of new-onset atrial fibrilation (AF) in patients with STEMI. This study enrolled 171 patients undergoing pPCI for STEMI. Among these patients 24 patients developed AF and the remaining 147 patients were designated as the controls. All clinical, demographical and laboratory parameters were entered into a dataset and compared between AF group and the controls. The presence of fQRS was higher in the AF group than in the controls (P=0.001). Diabetes mellitus and fQRS was significantly more common in the AF group (P=0.003 and P=0.001 respectively) Logistic regression analysis demonstrated that the presence of fQRS was the independent determinant of AF (OR: 3.243, 95% CI 1.016-10.251, P=0.042). Increased atrial fibrillation was observed more frequently in STEMI patients with fQRS than in patients without fQRS. fQRS is an important determinant of AF in STEMI after pPCI. Copyright © 2017 Elsevier Inc. All rights reserved.

Heart Rate at Hospital Discharge in Patients With Heart Failure Is Associated With Mortality and Rehospitalization

PubMed Central

Laskey, Warren K.; Alomari, Ihab; Cox, Margueritte; Schulte, Phillip J.; Zhao, Xin; Hernandez, Adrian F.; Heidenreich, Paul A.; Eapen, Zubin J.; Yancy, Clyde; Bhatt, Deepak L.; Fonarow, Gregg C.

2015-01-01

Background Whether heart rate upon discharge following hospitalization for heart failure is associated with long‐term adverse outcomes and whether this association differs between patients with sinus rhythm (SR) and atrial fibrillation (AF) have not been well studied. Methods and Results We conducted a retrospective cohort study from clinical registry data linked to Medicare claims for 46 217 patients participating in Get With The Guidelines®–Heart Failure. Cox proportional‐hazards models were used to estimate the association between discharge heart rate and all‐cause mortality, all‐cause readmission, and the composite outcome of mortality/readmission through 1 year. For SR and AF patients with heart rate ≥75, the association between heart rate and mortality (expressed as hazard ratio [HR] per 10 beats‐per‐minute increment) was significant at 0 to 30 days (SR: HR 1.30, 95% CI 1.22 to 1.39; AF: HR 1.23, 95% CI 1.16 to 1.29) and 31 to 365 days (SR: HR 1.15, 95% CI 1.12 to 1.20; AF: HR 1.05, 95% CI 1.01 to 1.08). Similar associations between heart rate and all‐cause readmission and the composite outcome were obtained for SR and AF patients from 0 to 30 days but only in the composite outcome for SR patients over the longer term. The HR from 0 to 30 days exceeded that from 31 to 365 days for both SR and AF patients. At heart rates <75, an association was significant for mortality only for both SR and AF patients. Conclusions Among older patients hospitalized with heart failure, higher discharge heart rate was associated with increased risks of death and rehospitalization, with higher risk in the first 30 days and for SR compared with AF. PMID:25904590

Role of homocysteine for thromboembolic complication in patients with non-valvular atrial fibrilation.

PubMed

Cingozbay, B Y; Yiginer, O; Cebeci, B S; Kardesoglu, E; Demiralp, E; Dincturk, M

2002-10-01

Thromboembolism is the most important complication in patients with atrial fibrilation (AF). Homocysteine is a toxic amino acid that has been recently accepted as a risk factor for atherosclerosis and stroke. The aim of the present study is to show whether there is a relation between hyperhomocysteinemia and thromboembolic complications in patients with non-valvular AF. We admitted 38 patients with non-valvular AF. The patients were divided into two groups: group A (n = 20; mean age, 75.7 +/- 10.4 years; three males/17 females), and group B (n = 18; mean age, 68.0 +/- 10.6 years; 11 males/seven females). While group A consisted of the patients with AF and stroke, group B was composed of the patients with AF but without stroke. The patients having sinus rhythm (15 subjects) were used as the reference group to obtain the cut-off value. Homocysteine was measured by the immunoassay method. The means of the homocysteine levels were 12.4 +/- 3.3 micromol/l in group A, 8.3 +/- 2.3 micromol/l in group B and 9.3 +/- 1.8 micromol/l in the reference group. The cut-off value was 10.6 micromol/l. Group A had a statistically higher homocysteine level than not only group B, but also the reference group (P < 0.05). While 60% of group A (n = 12) had the elevated homocysteine level, the rate was only 22% for group B (n = 4). In conclusion, hyperhomocysteinemia may be one of the explanations for the increased rate of thromboembolic complications in older patients with AF.

Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

NASA Technical Reports Server (NTRS)

Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

2009-01-01

Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

Pulmonary vein isolation alone and combined with renal sympathetic denervation in chronic kidney disease patients with refractory atrial fibrillation.

PubMed

Kiuchi, Márcio G; Chen, Shaojie; E Silva, Gustavo R; Paz, Luis M R; Kiuchi, Tetsuaki; de Paula Filho, Ary G; Souto, Gladyston L L

2016-12-01

Atrial fibrillation (AF) commonly occurs in association with chronic kidney disease (CKD), resulting in adverse outcomes. Combining pulmonary vein isolation (PVI) and renal sympathetic denervation (RSD) may reduce the recurrence of AF in patients with CKD and hypertension. We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity. Our goal was to compare the impact of PVI + RSD with that of PVI alone in patients with concurrent AF and CKD. This was a single-center, prospective, longitudinal, randomized, double-blind study. Forty-five patients with controlled hypertension, symptomatic paroxysmal AF and/or persistent AF, stage 2 or 3 CKD, and a dual-chamber pacemaker were enrolled from January 2014 to January 2015. We assessed the 30-second recurrence of AF recorded by the pacemaker, 24-hour ambulatory blood pressure measurements, estimated glomerular filtration rate, albuminuria, echocardiographic parameters, and safety of RSD. No patient developed procedural or other complications. The ambulatory blood pressure measurements did not differ within the PVI + RSD group or between the PVI + RSD and PVI groups throughout the study. Significantly more patients in the PVI + RSD group than in the PVI group were free of AF at the 12-month follow-up evaluation. The PVI group had an unacceptable response to ablation with respect to changes in echocardiographic parameters, whereas these parameters improved in the PVI + RSD group. PVI + RSD were associated with a lower AF recurrence rate than PVI alone; it also improved renal function and some echocardiographic parameters. These encouraging data will serve as baseline information for further long-term studies on larger patient populations.

Recognition of the 3′ splice site RNA by the U2AF heterodimer involves a dynamic population shift

PubMed Central

Voith von Voithenberg, Lena; Sánchez-Rico, Carolina; Kang, Hyun-Seo; Madl, Tobias; Zanier, Katia; Barth, Anders; Warner, Lisa R.; Sattler, Michael; Lamb, Don C.

2016-01-01

An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3′ splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3′ splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein–RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3′ splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants. PMID:27799531

Prevalence, Management, and Long-Term (6-Year) Outcomes of Atrial Fibrillation Among Patients Receiving Drug-Eluting Coronary Stents.

PubMed

Choi, Hyo-In; Ahn, Jung-Min; Kang, Se Hun; Lee, Pil Hyung; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Park, Duk-Woo; Park, Seung-Jung

2017-06-12

This study sought to investigate the incidence, management, and clinical relevance of atrial fibrillation (AF) during and after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and evaluate outcomes of different antithrombotic strategies. Uncertainty exists regarding the optimal antithrombotic strategy in patients with AF who are undergoing PCI with DES. Using a consecutive series of 10,027 patients who underwent DES implantation between 2003 and 2011, we evaluated the overall prevalence and clinical impact of AF. In addition, we compared the efficacy and safety of dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel) and triple therapy (DAPT plus warfarin) among patients with AF. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. Overall, 711 (7.1%) patients had a diagnosis of AF at the index PCI. Patients with AF were older, had more comorbid conditions, and more often had a history of strokes; most patients with AF (88.4%) received DAPT rather than triple therapy (10.5%) at discharge. The rate of primary outcome after PCI during the 6-year follow-up period was significantly higher in patients with AF than in those without AF (22.1% vs. 8.0%; p < 0.001). This trend was consistent for major bleeding (4.5% vs. 1.5%; p < 0.001). After multivariable adjustment, the presence of AF was significantly associated with a higher risk of primary outcome (hazard ratio [HR]: 2.33; 95% confidence interval [CI]: 1.95 to 2.79; p < 0.001) and major bleeding (HR: 2.01; 95% CI: 1.32 to 3.06; p = 0.001). Among patients with AF, adjusted risk for the primary outcome was similar between the DAPT group and the triple therapy group (HR: 1.01; 95% CI: 0.60 to 1.69; p = 0.98), but triple therapy was associated with a significantly higher risk of hemorrhagic stroke (HR: 7.73; 95% CI: 2.14 to 27.91; p = 0.002) and major bleeding (HR: 4.48; 95% CI: 1.81 to 11.08; p = 0.001). Among patients receiving DES

The association of plasma oxidative status and inflammation with the development of atrial fibrillation in patients presenting with ST elevation myocardial infarction.

PubMed

Bas, Hasan Aydin; Aksoy, Fatih; Icli, Atilla; Varol, Ercan; Dogan, Abdullah; Erdogan, Dogan; Ersoy, Ibrahim; Arslan, Akif; Ari, Hatem; Bas, Nihal; Sutcu, Recep; Ozaydin, Mehmet

2017-04-01

Atrial fibrillation (AF) is the most common supraventricular arrhythmia following ST elevation myocardial infarction (STEMI). Oxidative stress and inflammation may cause structural and electrical remodeling in the atria making these critical processes in the pathology of AF. In this study, we aimed to evaluate the association between total oxidative status (TOS), total antioxidative capacity (TAC) and high-sensitivity C-reactive protein (hs-CRP) in the development of AF in patients presenting with STEMI. This prospective cohort study consisted of 346 patients with STEMI. Serum TAC and TOS were assessed by Erel's method. Patients were divided into two groups: those with and those without AF. Predictors of AF were determined by multivariate regression analysis. In the present study, 9.5% of patients developed AF. In the patients with AF, plasma TOS and oxidative stress index (OSI) values were significantly higher and plasma TAC levels were significantly lower compared to those without AF (p = .003, p = .002, p < .0001, respectively). Multivariate regression analysis results showed that, female gender (Odds ratio [OR] = 3.07; 95% Confidence Interval [CI] = 1.26-7.47; p = .01), left atrial diameter (OR =1.28; 95% CI =1.12-1.47; p < .0001), hs-CRP (OR =1.02; 95% CI =1.00-1.03; p = .001) and OSI (OR =1.10; 95% CI =1.04-1.18; p = .001) were associated with the development of AF in patients presenting with STEMI. The main finding of this study is that oxidative stress and inflammation parameters were associated with the development of AF in patients presenting with STEMI. Other independent predictors of AF were female gender, left atrial diameter and hs-CRP.

The prevalence of oral anticoagulation in patients with atrial fibrillation in Portugal: Systematic review and meta-analysis of observational studies.

PubMed

Caldeira, Daniel; Barra, Márcio; David, Cláudio; Costa, João; Ferreira, Joaquim J; Pinto, Fausto J

2014-09-01

Oral anticoagulation (OAC) is an effective treatment in the prevention of thromboembolic events in patients with atrial fibrillation (AF). The aim of this review was to estimate the prevalence of OAC therapy in patients with AF in Portugal. MEDLINE, the Index of Portuguese Medical Journals and SIBUL (the Bibliographic Catalog of the Integrated Library System of the University of Lisbon) were searched for Portuguese observational studies reporting the proportion of anticoagulated patients with AF. The pooled estimated prevalence of anticoagulated patients and respective 95% confidence interval (CI) were determined by means of a meta-analysis. Seven studies were included for analysis, of which four were conducted in a hospital environment and three in the general community. These studies enrolled a total of 891 patients with AF. The pooled estimated prevalence of anticoagulated patients was 40% (95% CI: 32-48%). The prevalence of OAC in Portuguese AF patients is low. There is a need to promote change in OAC prescribing habits for AF patients in Portugal, in accordance with international guidelines. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced by Marine-Derived Aspergillus fumigatus R9.

PubMed

Rao, Qi; Guo, Wenbin; Chen, Xinhua

2015-05-01

A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 μg/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi.

Prevalence of atrial fibrillation and the HATCH score: Intensified monitoring of patients with high HATCH score.

PubMed

Tischer, Tina S; Schneider, Ralph; Lauschke, Jörg; Diedrich, Doreen; Kundt, Günther; Bänsch, Dietmar

2015-08-01

The HATCH score [hypertension, age > 75 years, previous transient ischemic attack (TIA) or stroke (doubled), chronic obstructive pulmonary disease, heart failure (doubled)] has been established to identify patients who are at risk of developing persistent forms of AF. We investigated whether this score is associated with the prevalence of AF in order to guide diagnostic efforts and therapy. The data of 150,408 consecutive patients who were hospitalized at the University Hospital of Rostock between 2007 and 2012 were analyzed. Factors constituting the HATCH score and the presence of AF were prospectively documented using ICD-10 admission codes. Patients were 67.6 ± 13.6 years of age with a mean HATCH score of 1.48 ± 1.02; 16 % had a history of AF and 4 % suffered a TIA or stroke. The prevalence of AF increased significantly with the HATCH score up to 60.0 % (p < 0.001). In all, 63 % of the patients had a HATCH score of 0 and 1 without any history of stroke. The HATCH score correlates with the occurrence of AF, since the prevalence of AF rises with rising score values. Therefore, the HATCH score may be used to select patients for intensified ECG monitoring. Moreover, the score may also be used for stroke risk assessment, as none of the patients with a low HATCH score suffered a stroke.

Upregulation of K(2P)3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation.

PubMed

Schmidt, Constanze; Wiedmann, Felix; Voigt, Niels; Zhou, Xiao-Bo; Heijman, Jordi; Lang, Siegfried; Albert, Virginia; Kallenberger, Stefan; Ruhparwar, Arjang; Szabó, Gábor; Kallenbach, Klaus; Karck, Matthias; Borggrefe, Martin; Biliczki, Peter; Ehrlich, Joachim R; Baczkó, István; Lugenbiel, Patrick; Schweizer, Patrick A; Donner, Birgit C; Katus, Hugo A; Dobrev, Dobromir; Thomas, Dierk

2015-07-14

Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K(2P)3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K(2P)) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K(2P)3.1 subunits exhibited predominantly atrial expression, and atrial K(2P)3.1 transcript levels were highest among functional K(2P) channels. K(2P)3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K(2P)3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K(2P)3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Enhancement of atrium-selective K(2P)3.1 currents contributes to APD shortening in patients with chronic AF, and K(2P)3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K(2P)3.1 as a novel drug target for mechanism-based AF therapy. © 2015 American Heart Association, Inc.

Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing

PubMed Central

Billon-Galés, Audrey; Krust, Andrée; Fontaine, Coralie; Abot, Anne; Flouriot, Gilles; Toutain, Céline; Berges, Hortense; Gadeau, Alain-Pierre; Lenfant, Françoise; Gourdy, Pierre; Chambon, Pierre; Arnal, Jean-François

2011-01-01

17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF20). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF20 to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF20 mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF20 in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF20 LDL-r−/− mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect. PMID:21788522

Cost-Effectiveness of Percutaneous Closure of the Left Atrial Appendage in Atrial Fibrillation Based on Results from PROTECT AF vs. PREVAIL

PubMed Central

Freeman, James V.; Hutton, David W.; Barnes, Geoffrey D.; Zhu, Ruo P.; Owens, Douglas K.; Garber, Alan M.; Go, Alan S.; Hlatky, Mark A.; Heidenreich, Paul A.; Wang, Paul J.; Al-Ahmad, Amin; Turakhia, Mintu P.

2016-01-01

Background Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost-effectiveness compared to anticoagulation has not been evaluated using all available contemporary trial data. Methods and Results We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost-effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of PROTECT AF and PREVAIL randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios (ICER) compared to warfarin and dabigatran were $20,486 and $23,422 per quality adjusted life year (QALY), respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 QALYs, respectively) and more costly. At a willingness-to-pay-threshold of $50,000 per QALY, LAA closure was cost-effective 90% and 9% of the time under PROTECT AF and PREVAIL assumptions, respectively. These results were sensitive to the rates of ischemic stroke and intracranial hemorrhage for LAA closure and medical anticoagulation. Conclusions Using data from the PROTECT AF trial, LAA closure with the Watchman device was cost-effective; using PREVAIL trial data, Watchman was more costly and less effective than warfarin and dabigatran. PROTECT AF enrolled more patients and has substantially longer follow-up time, allowing greater statistical certainty with the cost-effectiveness results. However, longer term trial results and post-marketing surveillance of major adverse events will be vital to determining the value of the Watchman in clinical practice. PMID:27307517

Atrial fibrillation in transcatheter aortic valve implantation patients: Incidence, outcome and predictors of new onset.

PubMed

Zweiker, David; Fröschl, Mario; Tiede, Stephanie; Weidinger, Paul; Schmid, Johannes; Manninger, Martin; Brussee, Helmut; Zweiker, Robert; Binder, Josepha; Mächler, Heinrich; Marte, Wolfgang; Maier, Robert; Luha, Olev; Schmidt, Albrecht; Scherr, Daniel

There is controversial evidence if atrial fibrillation (AF) alters outcome after transcatheter aortic valve implantation (TAVI). TAVI itself may promote new-onset AF (NOAF). We performed a single-center study including 398 consecutive patients undergoing TAVI. Before TAVI, patients were divided into a sinus rhythm (SR) group (n=226, 57%) and baseline AF group (n=172, 43%) according to clinical records and electrocardiograms. Furthermore, incidence and predictors of NOAF were recorded. Baseline AF patients had a significantly higher 1-year mortality than the baseline SR group (19.8% vs. 11.5%, p=0.02). NOAF occurred in 7.1% of patients with prior SR. Previous valve surgery was the only significant predictor of NOAF (HR 5.86 [1.04-32.94], p<0.05). NOAF was associated with higher rehospitalization rate (62.5 vs. 34.8%, p=0.04), whereas mortality was unaffected. This study shows that NOAF is associated with higher rates of rehospitalization but not mortality after TAVI. Overall, patients with pre-existing AF have higher mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Measuring Teachers' Assessment for Learning (AfL) Classroom Practices in Elementary Schools

ERIC Educational Resources Information Center

Lysaght, Zita; O'Leary, Michael; Ludlow, Larry

2017-01-01

Assessment for Learning (AfL) may be conceptualized as minute-to-minute, day-by-day interactions between learners and teachers with the improvement of learning as the principal focus. This paper traces the development of an AfL measurement instrument (scale) that can be used for research purposes prior to, during and following professional…

Identifying postoperative atrial fibrillation in cardiac surgical patients posthospital discharge, using iPhone ECG: a study protocol

PubMed Central

Lowres, Nicole; Freedman, S Ben; Gallagher, Robyn; Kirkness, Ann; Marshman, David; Orchard, Jessica; Neubeck, Lis

2015-01-01

Introduction Postoperative atrial fibrillation (AF) occurs in 30–40% of patients after cardiac surgery. Identification of recurrent postoperative AF is required to initiate evidence-based management to reduce the risk of subsequent stroke. However, as AF is often asymptomatic, recurrences may not be detected after discharge. This study determines feasibility and impact of a self-surveillance programme to identify recurrence of postoperative AF in the month of posthospital discharge. Methods and analysis This is a feasibility study, using a cross-sectional study design, of self-screening for AF using a hand-held single-lead iPhone electrocardiograph device (iECG). Participants will be recruited from the cardiothoracic surgery wards of the Royal North Shore Hospital and North Shore Private Hospital, Sydney, Australia. Cardiac surgery patients admitted in sinus rhythm and experiencing a transient episode of postoperative AF will be eligible for recruitment. Participants will be taught to take daily ECG recordings for 1 month posthospital discharge using the iECG and will be provided education regarding AF, including symptoms and health risks. The primary outcome is the feasibility of patient self-monitoring for AF recurrence using an iECG. Secondary outcomes include proportion of patients identified with recurrent AF; estimation of stroke risk and patient knowledge. Process outcomes and qualitative data related to acceptability of patient's use of the iECG and sustainability of the screening programme beyond the trial setting will also be collected. Ethics and dissemination Primary ethics approval was received on 25 February 2014 from Northern Sydney Local Health District Human Resource Ethics Committee, and on 17 July 2014 from North Shore Private Hospital Ethics Committee. Results will be disseminated via forums including, but not limited to, peer-reviewed publications and presentation at national and international conferences. Trial registration number ACTRN

Improving cost-effectiveness of and outcomes from drug therapy in patients with atrial fibrillation in managed care: role of the pharmacist.

PubMed

Johnson, Samuel G

2009-08-01

The medical care costs for procedures, medications, and testing associated with atrial fibrillation (AF) in the United States are high and projected to increase markedly in the future as the number of Americans affected grows. The burden on patient quality of life, the health care system, and society are pharmacoeconomic considerations in managing AF. To identify key pharmacoeconomic considerations in managing AF and describe ways in which managed care pharmacists can improve the cost-effectiveness of and outcomes from drug therapy for AF. The high medical care costs of AF are largely the result of the high cost of hospitalization and inpatient procedures. Recurrence of AF dramatically increases costs, especially for hospital care. Managed care pharmacists have many opportunities to provide cost-effective care to and improve outcomes in patients with AF. Policy and process review, population management, and case management are key strategies for improving outcomes in patients with AF. Pharmacist input into policy and process review, including pharmacy benefits design, formulary management, and the use of information technology, can help ensure that the use of drug therapy for AF is cost-effective. Population management strategies, such as development of clinical pathways and patient registries, seek to improve the quality, consistency, and cost-effectiveness of care and the likelihood that desired therapeutic outcomes are achieved through targeted interventions. Case management strategies focus on longitudinal care for individuals in order to improve quality. Pharmacist-managed anticoagulation services and antiarrhythmic drug monitoring are the 2 most widely known case management strategies for patients with AF. Managed care pharmacists can screen patients with AF for the use of anticoagulation, which is needed to prevent embolic stroke but is under-used, even though recommended by evidence-based guidelines. The clinical efficacy and cost-effectiveness of

A Qualitative and Quantitative Assessment of Fundus Autofluorescence Patterns in Patients With Choroideremia.

PubMed

Jolly, Jasleen K; Edwards, Thomas L; Moules, Jonathan; Groppe, Markus; Downes, Susan M; MacLaren, Robert E

2016-08-01

We set out to characterize the pattern of fundus autofluorescence (AF) loss in choroideremia (CHM) patients of varying ages and disease severity in order to determine the average rate of progression of this potential disease biomarker. Fifty consecutive CHM patients (100 eyes) attending outpatient clinics at Oxford Eye Hospital underwent analysis with the Heidelberg OCT Spectralis with autofluorescence capabilities. The area of residual AF was traced using Heidelberg Eye Explorer. Bland-Altman analysis was used to calculate the coefficient of repeatability (CR). The degree of AF loss was correlated to different ages and the pattern of residual AF constructed into color-coded maps in order to gain insight into the mechanism of disease progression. The CR for measurement of AF area is <1%, indicating that a small change is likely to be significant. Correlation of patient age and area of residual AF produced a clinically relevant index of expected anatomic disease. Progression is 7.7% of the residual area each year (95% confidence intervals 7.0%-8.2%) and follows a logarithmic pattern with age (r = 0.95, P < 0.001). From this we derived the mean half-life of AF as 9 years. Qualitatively, the pattern of remaining AF centered on a point temporal to the fovea. The area of residual AF in CHM can be measured reproducibly and shows a distinct pattern of loss. The measured residual area is inversely correlated to age. The ratio of the two variables may provide useful information regarding the rate of progression for any one individual at a given point in time.

Interatrial block and interatrial septal thickness in patients with paroxysmal atrial fibrillation undergoing catheter ablation: Long-term follow-up study.

PubMed

Gul, Enes E; Pal, Raveen; Caldwell, Jane; Boles, Usama; Hopman, Wilma; Glover, Benedict; Michael, Kevin A; Redfearn, Damian; Simpson, Chris; Abdollah, Hoshiar; Baranchuk, Adrian

2017-07-01

Interatrial block (IAB) is a strong predictor of recurrence of atrial fibrillation (AF). IAB is a conduction delay through the Bachman region, which is located in the upper region of the interatrial space. During IAB, the impulse travels from the right atrium to the interatrial septum (IAS) and coronary sinus to finally reach the left atrium in a caudocranial direction. No relation between the presence of IAB and IAS thickness has been established yet. To determine whether a correlation exists between the degree of IAB and the thickness of the IAS and to determine whether IAS thickness predicts AF recurrence. Sixty-two patients with diagnosis of paroxysmal AF undergoing catheter ablation were enrolled. IAB was defined as P-wave duration ≥120 ms. IAS thickness was measured by cardiac computed tomography. Among 62 patients with paroxysmal AF, 45 patients (72%) were diagnosed with IAB. Advanced IAB was diagnosed in 24 patients (39%). Forty-seven patients were male. During a mean follow-up period of 49.8 ± 22 months (range 12-60 months), 32 patients (51%) developed AF recurrence. IAS thickness was similar in patients with and without IAB (4.5 ± 2.0 mm vs. 4.0 ± 1.4 mm; p = .45) and did not predict AF. Left atrial size was significantly enlarged in patients with IAB (40.9 ± 5.7 mm vs. 37.2 ± 4.0 mm; p = .03). Advanced IAB predicted AF recurrence after the ablation (OR: 3.34, CI: 1.12-9.93; p = .03). IAS thickness was not significantly correlated to IAB and did not predict AF recurrence. IAB as previously demonstrated was an independent predictor of AF recurrence. © 2016 Wiley Periodicals, Inc.

Dementia correlates with anticoagulation underuse in older patients with atrial fibrillation.

PubMed

Viscogliosi, Giovanni; Ettorre, Evaristo; Chiriac, Iulia Maria

2017-09-01

Stroke prevention in older atrial fibrillation (AF) patients remains a challenge. This study aimed to investigate whether a dementia diagnosis is an independent correlate of lower prescription rate of oral anticoagulant treatment (OAT) in a sample of older AF patients. Cross-sectional retrospective study. Consecutive older community-dwelling AF patients referred for a comprehensive geriatric assessment, were considered. Evaluation of physical, social and mental health, and administration of the Cumulative Illness Rating Scale (CIRS) and Barthel Index were performed. Dementia cases were ascertained by consensus of 2 experienced geriatricians. Dementia severity was assessed using the Clinical Dementia Rating scale (CDR). 316 AF patients (ages 74.7±7.0years, 55.7% women) with high stroke risk (77.5% had a CHA 2 DS 2 VASC score ≥3), low bleeding and falling risk, and no neuropsychiatric/behavioral symptoms, were included. 60.1% were prescribed with OAT. Among patients with dementia (n=86, 27.2%), 22.0% received inadequate antithrombotic prophylaxis (i.e. antiplatelet) and 38.5% no treatment. Proportion of those receiving inadequate or no prophylaxis increased at increasing CDR score. By multiple regression models, either dementia (yes vs no), OR=1.33, 95%CI=1.11-1.46, p<0.001, and dementia severity (CDR>1), OR=2.38, 95%CI=2.19-2.60, p<0.001, were associated with lack of OAT prescription independently of age, paroxysmal AF, and comorbidity burden. Dementia might be associated with underuse of OAT in older AF patients even in the absence of established contraindications. Future studies are needed to assess the real dimension of the problem and clinician's barriers to prescribing OAT in demented patients. Copyright © 2017. Published by Elsevier B.V.

Predictive factors for bleeding during treatment with rivaroxaban and warfarin in Japanese patients with atrial fibrillation - Subgroup analysis of J-ROCKET AF.

PubMed

Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Cavaliere, Mary; Iekushi, Kazuma; Yamanaka, Satoshi

2016-12-01

Results from the J-ROCKET AF study revealed that rivaroxaban was non-inferior to warfarin with respect to the principal safety outcomes in patients with non-valvular atrial fibrillation. This subgroup analysis evaluated whether non-major clinically relevant bleeding (NMCRB) could be a predictive factor for major bleeding (MB). Other predictive factors for MB were also obtained in both rivaroxaban and warfarin treatment groups. The temporal incidence of MB was compared between the rivaroxaban and warfarin treatment groups. Assessment was made whether MB events were often preceded by NMCRB. Univariate and multivariate analyses were carried out to identify any independent predictive factors for MB in both treatment groups. The incidences of MB and NMCRB were 18.04% (138/639 patients) in the rivaroxaban arm, and 16.42% in the warfarin arm (124/639 patients). NMCRB preceded MB in only four patients in each treatment group (rivaroxaban: 4/117 and warfarin: 4/98). Multivariate analysis identified predictive factors for bleeding events: anemia with warfarin treatment and concomitant use of antiplatelet agents with rivaroxaban treatment. Results from this subgroup analysis, particularly the fact that there was no repeated or sequential pattern between NMCRB and MB occurrences in both treatment groups, suggests that NMCRB might not be a predictive factor for MB. On the contrary, anemia and concomitant use of antiplatelet therapy were likely predictive factors for bleeding with warfarin and rivaroxaban treatment, respectively. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Challenges of stroke prevention in patients with atrial fibrillation in clinical practice.

PubMed

Hobbs, F D Richard; Leach, I

2011-09-01

Strokes and transient ischaemic attacks in patients with atrial fibrillation (AF) can be largely prevented. Risk stratification and appropriate prophylactic regimens help to alleviate the burden of AF-related thromboembolism. Guidelines recommend routine anticoagulation with oral vitamin K antagonists (VKAs) for patients at moderate-to-high risk of stroke, and acetylsalicylic acid (ASA) for those at low risk of stroke. ASA is less effective at reducing the risk of stroke than VKAs; however, ASA does not require monitoring or dose adjustment. Trials of anticoagulants show consistent benefits of oral VKAs for primary and secondary stroke prevention in patients with AF. Nevertheless, VKAs do require frequent coagulation monitoring and dose adjustment because of their variable dose-response profile, narrow therapeutic window, increased risk for bleeding complications and numerous food and drug interactions. This review aims to provide an overview of the clinical challenges of anticoagulant therapy for the prevention of stroke in patients with AF.

Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China.

PubMed

Yang, Xiaomeng; Li, Shuya; Zhao, Xingquan; Liu, Liping; Jiang, Yong; Li, Zixiao; Wang, Yilong; Wang, Yongjun

2017-12-04

Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF. Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis. Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR = 4.70, 95%CI, 1.64-13.5), advanced age (OR = 1.06, 95%CI, 1.04-1.09), NIHSS at admission (OR = 1.06, 95%CI, 1.02-1.10), blood high density lipoprotein (HDL) (OR = 1.52, 95%CI, 1.09-2.13), together with blood triglycerides (OR = 0.64, 95%CI, 0.45-0.91) were independently associated with newly-detected AF. Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF. NCT02156765 (June 5, 2014).

Delayed Anaerobic Threshold in Heart Failure Patients With Atrial Fibrillation.

PubMed

Palermo, Pietro; Magrì, Damiano; Sciomer, Susanna; Stefanini, Elisa; Agalbato, Cecilia; Compagnino, Elisa; Chircu, Cristina M; Maffessanti, Francesco; Teodoru, Minodora; Agostoni, Piergiuseppe

2016-01-01

To assess whether atrial fibrillation (AF) in heart failure (HF) affects oxygen uptake at anaerobic threshold ((Equation is included in full-text article.)O2 AT) and heart rate (HR) kinetics. A total of 15 patients with HF and AF and 18 with HF and sinus rhythm (SR) performed a maximal incremental and 2 constant workload cycle ergometer cardiopulmonary exercise tests (below and above AT, at 25% and 75% of maximal workload, respectively). At constant workload tests, kinetics of (Equation is included in full-text article.)O2 and HR were assessed by calculating time constant (τ). HF patients with AF showed a similar peak (Equation is included in full-text article.)O2 to those with SR (16.7 ± 4.5 mL/kg/min vs 16.6 ± 3.9 mL/kg/min). However, (Equation is included in full-text article.)O2 AT (11.3 ± 2.9 mL/kg/min vs 9.3 ± 2.8 mL/kg/min; P < .05), peak HR (149 ± 18.8 bpm vs 116.4 ± 20.4 bpm; P < .001), HR AT (125.3 ± 19.1 bpm vs 90.3 ± 15.5 bpm; P < .001), and HR increase during exercise were greater in HF patients with AF. Finally, τHR and τ(Equation is included in full-text article.)O2 below and above AT were not significantly different. In HF patients with AF, despite a similar peak (Equation is included in full-text article.)O2 compared with patients with HF and SR, (Equation is included in full-text article.)O2 AT is higher because of a higher HR and a greater HR increase during exercise. One postulated mechanism would be a greater cardiac output increase at the beginning of exercise in HF patients with AF. The delayed AT generates uncertainty about the meaning of a (Equation is included in full-text article.)O2 value at AT in HF patients with AF, because a higher AT is usually associated with better performance and a better prognosis.

Effectiveness of atrial fibrillation as an independent predictor of death and coronary events in patients having coronary angiography.

PubMed

Marte, Thomas; Saely, Christoph H; Schmid, Fabian; Koch, Lorena; Drexel, Heinz

2009-01-01

The impact of atrial fibrillation (AF) on future coronary events is uncertain. In particular, the prognostic impact of AF in the clinically important population of coronary patients who undergo angiography is unknown. The aim of this study was to investigate (1) the prevalence of AF, (2) its association with coronary atherosclerosis, and (3) its impact on future coronary events in patients who undergo angiography. Electrocardiograms were evaluated in a consecutive series of 613 patients who underwent coronary angiography. Prospectively, death and cardiovascular events were recorded over 4.0 +/- 0.6 years. Among these patients, 37 (6%) at baseline had AF, and 576 (94%) were in sinus rhythm. The presence of AF was associated with a lower prevalence of coronary artery disease and of coronary diameter narrowing >or=50% on baseline angiography. However, prospectively, patients with AF were at a strongly increased risk for all-cause mortality (adjusted hazard ratio 5.15, 95% confidence interval 2.36 to 11.26, p <0.001), coronary death (hazard ratio 8.16, 95% confidence interval 2.89 to 23.09, p <0.001), and major coronary events (hazard ratio 3.80, 95% confidence interval 1.45 to 9.94, p = 0.007). In conclusion, although inversely associated with the presence of angiographically determined coronary atherosclerosis, AF is a strong predictor of death and future coronary events in patients with coronary artery disease who undergo coronary angiography.

Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension: a subgroup analysis of the J-ROCKET AF trial.

PubMed

Matsumoto, Masayasu; Hori, Masatsugu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

2014-05-01

The majority of the patients enrolled in the rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial had hypertension. In this subgroup analysis, we investigated differences in the safety and efficacy of rivaroxaban and warfarin in subjects with and without hypertension. The baseline blood pressure (BP) measurements of patients with hypertension in the rivaroxaban and warfarin groups were 130/77 mm Hg and 131/77 mm Hg, respectively, whereas those of patients without hypertension were 123/74 mm Hg and 124/73 mm Hg, respectively. The incidence rates of the principal safety outcomes in the rivaroxaban and warfarin groups were 18.39% per year and 16.81% per year, respectively, among patients with baseline hypertension (hazard ratio (HR): 1.10; 95% confidence interval (CI): 0.84-1.45) and 16.71% per year and 15.00% per year, respectively, among patients without hypertension at baseline (HR: 1.14; 95% CI: 0.66-1.97), indicating no significant interaction (P=0.933). The incidence rates of the primary efficacy endpoints in the rivaroxaban group and the warfarin group were 0.54% per year and 2.24% per year, respectively, in patients without baseline hypertension (HR: 0.25; 95% CI: 0.03-2.25), and 1.45% per year and 2.71% per year, respectively, in patients with baseline hypertension (HR: 0.54; 95% CI: 0.25-1.16), indicating no significant interaction (P=0.509). In conclusion, the safety and efficacy profile of rivaroxaban was similar to that of warfarin, independent of baseline hypertensive status.

Usefulness of severe cardiac sympathetic dysfunction to predict the occurrence of rapid atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

PubMed

Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Asano, Taku; Suyama, Jumpei; Tanno, Kaoru; Namiki, Atsuo; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

2013-09-01

Atrial fibrillation (AF) can be a potentially life-threatening arrhythmia when it conducts rapidly through the accessory pathway, which was not predicted by the noninvasive method. We evaluated the cardiac sympathetic activity for predicting the occurrence of AF in patients with Wolff-Parkinson-White (WPW) syndrome. Iodine-123 metaiodobenzylguanidine scintigraphy was performed under stable sinus rhythm conditions at rest <1 week before an electrophysiologic study (EPS) to assess the sympathetic activity using the heart/mediastinum (H/M) ratio in 45 consecutive patients with WPW who had a history of supraventricular tachycardia (mean ± SD, age: 47 ± 17 years, 42.2% women). The study also included 15 normal healthy volunteers (56 ± 17 years, 40% women). The H/M ratio was lower in patients with WPW syndrome than in the normal control group, and in the 15 patients with AF induced during EPS than in the 30 patients without AF (p <0.0001). The sensitivity of H/M ratio ≤2.8 for predicting the AF induced during EPS was 75% in 12 of 16 patients, and the specificity was 89.7% in 26 of 29 patients. The H/M ratio was positively correlated with anterograde effective refractory period (r = 0.514, p <0.0001). The sensitivity of H/M ratio ≤2.75 for predicting the AF with a short anterograde effective refractory period (≤250 ms) was 91.7% in 11 of 12 patients, and the specificity was 90.9% in 30 of 33 patients. In conclusion, the severe cardiac sympathetic dysfunction was associated with the occurrence of AF, particularly in those with rapid AF and in patients with WPW syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison of Microlife BP A200 Plus and Omron M6 blood pressure monitors to detect atrial fibrillation in hypertensive patients.

PubMed

Marazzi, Giuseppe; Iellamo, Ferdinando; Volterrani, Maurizio; Lombardo, Mauro; Pelliccia, Francesco; Righi, Daniela; Grieco, Fabrizia; Cacciotti, Luca; Iaia, Luigi; Caminiti, Giuseppe; Rosano, Giuseppe

2012-01-01

Self-monitoring home blood pressure (BP) devices are currently recommended for long-term follow-up of hypertension and its management. Some of these devices are integrated with algorithms aimed at detecting atrial fibrillation (AF), which is common essential hypertension. This study was designed to compare the diagnostic accuracy of two widely diffused home BP monitoring devices in detecting AF in an unselected population of outpatients referred to a hypertension clinic because of high BP. In 503 consecutive patients the authors simultaneously compared the accuracy of the Microlife(®) BP A200 Plus (Microlife) and the OMRON(®) M6 (OMRON) home BP devices, in detecting AF. Systolic and diastolic BP as well as heart rate (HR) values detected by the two devices were not significantly different. Pulse irregularity was detected in 124 and 112 patients with the OMRON M6 and Microlife BP A200 Plus devices, respectively. Simultaneous electrocardiogram (ECG) recording revealed that pulse irregularity was due to AF in 101 patients. Pulse irregularity detected by the OMRON M6 device corresponded to AF in 101, to supraventricular premature beats in 18, and to frequent premature ventricular beat in five patients, respectively. Pulse irregularity detected by the Microlife BP A200 Plus device corresponded to AF in 93, to supraventricular premature beats in 14, and to ventricular premature beats in five patients. The sensitivity for detecting AF was 100%, the specificity was 92%, and diagnostic accuracy 95% for the OMRON M6 and 100%, 92%, and 95 for the Microlife BP A200 Plus, respectively. AF was newly diagnosed by ECG recordings in 47 patients, and was detected in all patients by the OMRON device, and in 42 patients by the Microlife device. These results indicate that OMRON M6 is more accurate than Microlife BP A200 Plus in detecting AF in patients with essential hypertension. Widespread use of these devices in hypertensive patients could be of clinical benefit for the early

Complete molecular remission in relapsed and refractory acute myeloid leukaemia with MLL-AF9 treated with chidamide-based chemotherapy.

PubMed

Lun, Y; Yang, J-J; Wu, Y

2017-12-01

The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy. Chidamide (CS055/HBI-8000) is a new histone deacetylase (HDAC) inhibitor that is clinically active in relapsed and refractory peripheral T-cell lymphomas. To the best of our knowledge, successful reinduction treatment on relapsed MLL-AF9 by chidamide-based regimen has not been previously reported. © 2017 John Wiley & Sons Ltd.

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation.

PubMed

Kristensen, Søren Lund; Jhund, Pardeep S; Mogensen, Ulrik M; Rørth, Rasmus; Abraham, William T; Desai, Akshay; Dickstein, Kenneth; Rouleau, Jean L; Zile, Michael R; Swedberg, Karl; Packer, Milton; Solomon, Scott D; Køber, Lars; McMurray, John J V

2017-10-01

Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without ( P <0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P <0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and ≥3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; ≥3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found

Features of intrinsic ganglionated plexi in both atria after extensive pulmonary isolation and their clinical significance after catheter ablation in patients with atrial fibrillation.

PubMed

Kurotobi, Toshiya; Shimada, Yoshihisa; Kino, Naoto; Ito, Kazato; Tonomura, Daisuke; Yano, Kentaro; Tanaka, Chiharu; Yoshida, Masataka; Tsuchida, Takao; Fukumoto, Hitoshi

2015-03-01

The features of intrinsic ganglionated plexi (GP) in both atria after extensive pulmonary vein isolation (PVI) and their clinical implications have not been clarified in patients with atrial fibrillation (AF). The purpose of this study was to assess the features of GP response after extensive PVI and to evaluate the relationship between GP responses and subsequent AF episodes. The study population consisted of 216 consecutive AF patients (104 persistent AF) who underwent an initial ablation. We searched for the GP sites in both atria after an extensive PVI. GP responses were determined in 186 of 216 patients (85.6%). In the left atrium, GP responses were observed around the right inferior GP in 116 of 216 patients (53.7%) and around the left inferior GP in 57 of 216 (26.4%). In the right atrium, GP responses were observed around the posteroseptal area: inside the CS in 64 of 216 patients (29.6%), at the CS ostium in 150 of 216 (69.4%), and in the lower right atrium in 45 of 216 (20.8%). The presence of a positive GP response was an independent risk factor for AF recurrence (hazard ratio 4.04, confidence interval 1.48-11.0) in patients with paroxysmal, but not persistent, AF. The incidence of recurrent atrial tachyarrhythmias in patients with paroxysmal AF with a positive GP response was 51% vs 8% in those without a GP response (P = .002). The presence of GP responses after extensive PVI was significantly associated with increased AF recurrence after ablation in patients with paroxysmal AF. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

PubMed

Goto, Koji; Nakai, Kentaro; Shizuta, Satoshi; Morimoto, Takeshi; Shiomi, Hiroki; Natsuaki, Masahiro; Yahata, Mitsuhiko; Ota, Chihiro; Ono, Koh; Makiyama, Takeru; Nakagawa, Yoshihisa; Furukawa, Yutaka; Kadota, Kazushige; Takatsu, Yoshiki; Tamura, Takashi; Takizawa, Akinori; Inada, Tsukasa; Doi, Osamu; Nohara, Ryuji; Matsuda, Mitsuo; Takeda, Teruki; Kato, Masayuki; Shirotani, Manabu; Eizawa, Hiroshi; Ishii, Katsuhisa; Lee, Jong-Dae; Takahashi, Masaaki; Horie, Minoru; Takahashi, Mamoru; Miki, Shinji; Aoyama, Takeshi; Suwa, Satoru; Hamasaki, Shuichi; Ogawa, Hisao; Mitsudo, Kazuaki; Nobuyoshi, Masakiyo; Kita, Toru; Kimura, Takeshi

2014-07-01

The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ≥2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ≥65%. Cumulative 5-year incidence of stroke in patients with TTR ≥65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Two years outcome in patients with persistent atrial fibrillation after pulmonary vein isolation using the second-generation 28-mm cryoballoon.

PubMed

Tscholl, Verena; Lsharaf, Abdullah Khaled-A; Lin, Tina; Bellmann, Barbara; Biewener, Sebastian; Nagel, Patrick; Suhail, Saba; Lenz, Klaus; Landmesser, Ulf; Roser, Mattias; Rillig, Andreas

2016-09-01

The efficacy of the second-generation cryoballoon (CB) in patients with paroxysmal atrial fibrillation (AF) has been demonstrated previously. Data on the efficacy of CB ablation in patients with persistent AF are sparse. The aim of this study was to evaluate the 2-year success rate of pulmonary vein isolation in patients with persistent AF using the second-generation CB. Fifty consecutive patients (mean age 64.6 ± 9.9 years; 19 women [38%]) with persistent AF were included in this analysis. The mean follow-up period was 22 ± 11 months. All patients were ablated using the second-generation 28-mm CB. Isolation of the pulmonary veins was confirmed using a spiral mapping catheter. In all patients, follow-up was obtained using 24-hour Holter monitoring or via interrogation of an implanted loop recorder or pacemaker. The mean left atrial diameter was 43.6 ± 5.6 mm, the mean CHA2DS2-VASc score was 2.8 ± 1.5, and the mean HAS-BLED score was 2.1 ± 1.2. The mean fluoroscopy time was 25.8 ± 9 minutes, and the mean procedural time was 146.4 ± 37.8 minutes. After 22 ± 11 months, the frequency of arrhythmia recurrence was 22 of 50 (44%) in the overall group (paroxysmal AF 6 of 22 [27%]; persistent AF 16 of 22 [73%]). No major complications occurred. Aneurysma spurium not requiring surgical intervention occurred in 1 (2%) patient. No phrenic nerve palsy was observed. Two years' results after pulmonary vein isolation using the second-generation CB in patients with persistent AF are promising. The clinical success rate appears to be similar to the reported success rates of radiofrequency ablation for the treatment of persistent AF. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Assessment of a personalized and distributed patient guidance system.

PubMed

Peleg, Mor; Shahar, Yuval; Quaglini, Silvana; Broens, Tom; Budasu, Roxana; Fung, Nick; Fux, Adi; García-Sáez, Gema; Goldstein, Ayelet; González-Ferrer, Arturo; Hermens, Hermie; Hernando, M Elena; Jones, Val; Klebanov, Guy; Klimov, Denis; Knoppel, Daniel; Larburu, Nekane; Marcos, Carlos; Martínez-Sarriegui, Iñaki; Napolitano, Carlo; Pallàs, Àngels; Palomares, Angel; Parimbelli, Enea; Pons, Belén; Rigla, Mercedes; Sacchi, Lucia; Shalom, Erez; Soffer, Pnina; van Schooten, Boris

2017-05-01

The MobiGuide project aimed to establish a ubiquitous, user-friendly, patient-centered mobile decision-support system for patients and for their care providers, based on the continuous application of clinical guidelines and on semantically integrated electronic health records. Patients would be empowered by the system, which would enable them to lead their normal daily lives in their regular environment, while feeling safe, because their health state would be continuously monitored using mobile sensors and self-reporting of symptoms. When conditions occur that require medical attention, patients would be notified as to what they need to do, based on evidence-based guidelines, while their medical team would be informed appropriately, in parallel. We wanted to assess the system's feasibility and potential effects on patients and care providers in two different clinical domains. We describe MobiGuide's architecture, which embodies these objectives. Our novel methodologies include a ubiquitous architecture, encompassing a knowledge elicitation process for parallel coordinated workflows for patients and care providers; the customization of computer-interpretable guidelines (CIGs) by secondary contexts affecting remote management and distributed decision-making; a mechanism for episodic, on demand projection of the relevant portions of CIGs from a centralized, backend decision-support system (DSS), to a local, mobile DSS, which continuously delivers the actual recommendations to the patient; shared decision-making that embodies patient preferences; semantic data integration; and patient and care provider notification services. MobiGuide has been implemented and assessed in a preliminary fashion in two domains: atrial fibrillation (AF), and gestational diabetes Mellitus (GDM). Ten AF patients used the AF MobiGuide system in Italy and 19 GDM patients used the GDM MobiGuide system in Spain. The evaluation of the MobiGuide system focused on patient and care providers

Identifying postoperative atrial fibrillation in cardiac surgical patients posthospital discharge, using iPhone ECG: a study protocol.

PubMed

Lowres, Nicole; Freedman, S Ben; Gallagher, Robyn; Kirkness, Ann; Marshman, David; Orchard, Jessica; Neubeck, Lis

2015-01-13

Postoperative atrial fibrillation (AF) occurs in 30-40% of patients after cardiac surgery. Identification of recurrent postoperative AF is required to initiate evidence-based management to reduce the risk of subsequent stroke. However, as AF is often asymptomatic, recurrences may not be detected after discharge. This study determines feasibility and impact of a self-surveillance programme to identify recurrence of postoperative AF in the month of posthospital discharge. This is a feasibility study, using a cross-sectional study design, of self-screening for AF using a hand-held single-lead iPhone electrocardiograph device (iECG). Participants will be recruited from the cardiothoracic surgery wards of the Royal North Shore Hospital and North Shore Private Hospital, Sydney, Australia. Cardiac surgery patients admitted in sinus rhythm and experiencing a transient episode of postoperative AF will be eligible for recruitment. Participants will be taught to take daily ECG recordings for 1 month posthospital discharge using the iECG and will be provided education regarding AF, including symptoms and health risks. The primary outcome is the feasibility of patient self-monitoring for AF recurrence using an iECG. Secondary outcomes include proportion of patients identified with recurrent AF; estimation of stroke risk and patient knowledge. Process outcomes and qualitative data related to acceptability of patient's use of the iECG and sustainability of the screening programme beyond the trial setting will also be collected. Primary ethics approval was received on 25 February 2014 from Northern Sydney Local Health District Human Resource Ethics Committee, and on 17 July 2014 from North Shore Private Hospital Ethics Committee. Results will be disseminated via forums including, but not limited to, peer-reviewed publications and presentation at national and international conferences. ACTRN12614000383662. Published by the BMJ Publishing Group Limited. For permission to use

Design and position control of AF lens actuator for mobile phone using IPMC-EMIM

NASA Astrophysics Data System (ADS)

Kim, Sung-Joo; Kim, Chul-Jin; Park, No-Cheol; Yang, Hyun-Seok; Park, Young-Pil; Park, Kang-Ho; Lee, Hyung-Kun; Choi, Nak-Jin

2008-03-01

IPMC-EMIM (Ionic Polyer Metal Composites + 1-ethyl-3- methyl imidazolium trifluromethane sulfonate, EMIM-Tfo) is fabricated by substituting ionic liquid for water in Nafion film, which improves water sensitiveness of IPMC and guarantees uniform performance regardless of the surrounding environment. In this paper, we will briefly introduce the procedure of fabrication of IPMC-EMIM and proceed to introduce the Hook-type actuator using IPMC-EMIM and application to AF Lens actuator. Parameters of Hook-type actuator are estimated from experimental data. In the simulation, The proposed AF Lens Actuator is assumed to be a linear system and based on estimated parameters, PID controller will be designed and controlled motion of AF Lens actuator will be shown through simulation.

A simple web-based tool to compare freshwater fish data collected using AFS standard methods

USGS Publications Warehouse

Bonar, Scott A.; Mercado-Silva, Norman; Rahr, Matt; Torrey, Yuta T.; Cate, Averill

2016-01-01

The American Fisheries Society (AFS) recently published Standard Methods for Sampling North American Freshwater Fishes. Enlisting the expertise of 284 scientists from 107 organizations throughout Canada, Mexico, and the United States, this text was developed to facilitate comparisons of fish data across regions or time. Here we describe a user-friendly web tool that automates among-sample comparisons in individual fish condition, population length-frequency distributions, and catch per unit effort (CPUE) data collected using AFS standard methods. Currently, the web tool (1) provides instantaneous summaries of almost 4,000 data sets of condition, length frequency, and CPUE of common freshwater fishes collected using standard gears in 43 states and provinces; (2) is easily appended with new standardized field data to update subsequent queries and summaries; (3) compares fish data from a particular water body with continent, ecoregion, and state data summaries; and (4) provides additional information about AFS standard fish sampling including benefits, ongoing validation studies, and opportunities to comment on specific methods. The web tool—programmed in a PHP-based Drupal framework—was supported by several AFS Sections, agencies, and universities and is freely available from the AFS website and fisheriesstandardsampling.org. With widespread use, the online tool could become an important resource for fisheries biologists.

27. "SITE PLAN." Specifications No. OC15775, Drawing No. AF600915, sheet ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

27. "SITE PLAN." Specifications No. OC1-57-75, Drawing No. AF-60-09-15, sheet 1 of 96, D.O. Series No. AF 1394/20, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract no. 5296 Rev. B, Date: 11/17/59. Site plan of 20,000-foot track, including construction phasing notes. - Edwards Air Force Base, South Base Sled Track, Edwards Air Force Base, North of Avenue B, between 100th & 140th Streets East, Lancaster, Los Angeles County, CA

ANMCO/AIAC/SICI-GISE/SIC/SICCH Consensus Document: percutaneous occlusion of the left atrial appendage in non-valvular atrial fibrillation patients: indications, patient selection, staff skills, organisation, and training

PubMed Central

Gulizia, Michele Massimo; Molon, Giulio; Mazzone, Patrizio; Audo, Andrea; Casolo, Giancarlo; Di Lorenzo, Emilio; Portoghese, Michele; Pristipino, Christian; Ricci, Renato Pietro; Themistoclakis, Sakis; Padeletti, Luigi; Tondo, Claudio; Berti, Sergio; Oreglia, Jacopo Andrea; Gerosa, Gino; Zanobini, Marco; Ussia, Gian Paolo; Musumeci, Giuseppe; Romeo, Francesco; Di Bartolomeo, Roberto

2017-01-01

Abstract Atrial fibrillation (AF) is the most common arrhythmia and its prevalence is increasing due to the progressive aging of the population. About 20% of strokes are attributable to AF and AF patients are at five-fold increased risk of stroke. The mainstay of treatment of AF is the prevention of thromboembolic complications with oral anticoagulation therapy. Drug treatment for many years has been based on the use of vitamin K antagonists, but recently newer and safer molecules have been introduced (dabigatran etexilate, rivaroxaban, apixaban, and edoxaban). Despite these advances, many patients still do not receive adequate anticoagulation therapy because of contraindications (relative and absolute) to this treatment. Over the last decade, percutaneous closure of left atrial appendage, main site of thrombus formation during AF, proved effective in reducing thromboembolic complications, thus offering a valid medical treatment especially in patients at increased bleeding risk. The aim of this consensus document is to review the main aspects of left atrial appendage occlusion (selection and multidisciplinary assessment of patients, currently available methods and devices, requirements for centres and operators, associated therapies and follow-up modalities) having as a ground the significant evolution of techniques and the available relevant clinical data. PMID:28751849

Determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation and preserved left ventricular ejection fraction.

PubMed

Letsas, Konstantinos P; Filippatos, Gerasimos S; Pappas, Loukas K; Mihas, Constantinos C; Markou, Virginia; Alexanian, Ioannis P; Efremidis, Michalis; Sideris, Antonios; Maisel, Alan S; Kardaras, Fotios

2009-02-01

The present study aimed to investigate the clinical and echocardiographic determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation (AF) and preserved left ventricular ejection fraction (LVEF). NT-pro-BNP levels were measured in 45 patients with paroxysmal AF, 41 patients with permanent AF and 48 controls. NT-pro-BNP levels were found significantly elevated in patients with paroxysmal (215+/-815 pg/ml) and permanent AF (1,086+/-835 pg/ml) in relation to control population (86.3+/-77.9 pg/ml) (P<0.001). According to the univariate linear regression analysis, age, hypertension, beta-blocker use, left atrial diameter (LAD), LVEF and AF status (paroxysmal or permanent or both) were significantly associated with NT-pro-BNP levels (P<0.05). In multiple linear regression analysis, LVEF (B coefficient: -53.030; CI: -95.738 to -10.322; P: 0.015) and LAD (B coefficient: 285.858; CI: 23.731-547.986; P: 0.033) were significant and independent determinants of NT-pro-BNP levels. Plasma NT-pro-BNP levels were significantly higher in patients with paroxysmal and permanent AF compared to those with sinus rhythm in the setting of preserved left ventricular systolic function. LVEF and LAD were independent predictors of NT-pro-BNP levels.

Transient spontaneous remission in congenital MLL-AF10 rearranged acute myeloid leukemia presenting with cardiorespiratory failure and meconium ileus.

PubMed

Gyárfás, Tobias; Wintgens, Juergen; Biskup, Wolfgang; Oschlies, Ilske; Klapper, Wolfram; Siebert, Reiner; Bens, Susanne; Haferlach, Claudia; Meisel, Roland; Kuhlen, Michaela; Borkhardt, Arndt

2016-12-01

Neonatal leukemia is a rare disease with an estimated prevalence of about one to five in a million neonates. The majority being acute myeloid leukemia (AML), neonatal leukemia can present with a variety of symptoms including hyperleucocytosis, cytopenia, hepatosplenomegaly, and skin infiltrates. Chromosomal rearrangements including mixed lineage leukemia (MLL) translocations are common in neonatal AML. A female neonate born at 34 weeks gestation presented with cardiorespiratory failure, hepatosplenomegaly, pancytopenia, and coagulopathy. She required intensive care treatment including mechanical ventilation, high-dose catecholamine therapy, and multiple transfusions. Small intestinal biopsy obtained during laparotomy for meconium ileus revealed an infiltrate by an undifferentiated monoblastic, MLL-rearranged leukemia. No other manifestations of leukemia could be detected. After spontaneous clinical remission, lasting 5 months without any specific treatment, the patient presented with leukemia cutis and full-blown monoblastic leukemia. MLL-AF10-rearranged AML could be re-diagnosed and successfully treated with chemotherapy and hematopoietic stem cell transplantation. Our patient exhibited a unique manifestation of neonatal MLL-AF10 rearranged AML with cardiorespiratory failure and intestinal infiltration. It highlights the importance of leukemia in the differential diagnosis of neonatal distress, congenital hematological abnormalities, and skin lesions.

Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

PubMed

Jalota, A; Scarabelli, T M; Saravolatz, L; Bakhsh, M U; Agrawal, P; Jalota, R; Chen-Scarabelli, C; Fuster, V; Halperin, J

2014-06-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

Impact of Body Mass Index on Plasma N-Terminal ProB-Type Natriuretic Peptides in Chinese Atrial Fibrillation Patients without Heart Failure

PubMed Central

Zheng, Li-hui; Wu, Ling-min; Yao, Yan; Chen, Wen-sheng; Bao, Jing-ru; Huang, Wen; Shi, Rui; Zhang, Kui-jun; Zhang, Shu

2014-01-01

Background An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure. Methods A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m2) and normal weight (BMI<25 kg/m2) patients. Results Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level. Conclusions An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients. PMID:25144363

Predictive value of CHADS2 and CHA2DS2-VASc scores for acute myocardial infarction in patients with atrial fibrillation.

PubMed

Pang, Hui; Han, Bing; Fu, Qiang; Zong, Zhenkun

2017-07-05

The presence of acute myocardial infarction (AMI) confers a poor prognosis in atrial fibrillation (AF), associated with increased mortality dramatically. This study aimed to evaluate the predictive value of CHADS 2 and CHA 2 DS 2 -VASc scores for AMI in patients with AF. This retrospective study enrolled 5140 consecutive nonvalvular AF patients, 300 patients with AMI and 4840 patients without AMI. We identified the optimal cut-off values of the CHADS 2 and CHA 2 DS 2 -VASc scores each based on receiver operating characteristic curves to predict the risk of AMI. Both CHADS 2 score and CHA 2 DS 2 -VASc score were associated with an increased odds ratio of the prevalence of AMI in patients with AF, after adjustment for hyperlipidaemia, hyperuricemia, hyperthyroidism, hypothyroidism and obstructive sleep apnea. The present results showed that the area under the curve (AUC) for CHADS 2 score was 0.787 with a similar accuracy of the CHA 2 DS 2 -VASc score (AUC 0.750) in predicting "high-risk" AF patients who developed AMI. However, the predictive accuracy of the two clinical-based risk scores was fair. The CHA 2 DS 2 -VASc score has fair predictive value for identifying high-risk patients with AF and is not significantly superior to CHADS 2 in predicting patients who develop AMI.

XANTUS: rationale and design of a noninterventional study of rivaroxaban for the prevention of stroke in patients with atrial fibrillation

PubMed Central

Camm, A John; Amarenco, Pierre; Haas, Sylvia; Hess, Susanne; Kirchhof, Paulus; van Eickels, Martin; Turpie, Alexander GG

2014-01-01

Atrial fibrillation (AF) is associated with a fivefold increase in the risk of stroke. The Phase III ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial showed that rivaroxaban, an oral, direct Factor Xa inhibitor, was noninferior to warfarin for the reduction of stroke or systemic embolism in patients with AF. Compared with warfarin, rivaroxaban significantly reduced rates of intracranial and fatal hemorrhages, although not rates of bleeding overall. XANTUS (Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation) is a prospective, international, observational, postauthorization, noninterventional study designed to collect safety and efficacy data on the use of rivaroxaban for stroke prevention in AF in routine clinical practice. The key goal is to determine whether the safety profile of rivaroxaban established in ROCKET AF is also observed in routine clinical practice. XANTUS is designed as a single-arm cohort study to minimize selection bias, and will enroll approximately 6,000 patients (mostly from Europe) with nonvalvular AF prescribed rivaroxaban, irrespective of their level of stroke risk. Overall duration of follow-up will be 1 year; the first patient was enrolled in June 2012. Similar studies (XANTUS-EL [Xarelto® for Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation, Eastern Europe, Middle East, Africa and Latin America] and XANAP [Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific]) are ongoing in Latin America and Asia-Pacific. Data from these studies will supplement those from ROCKET AF and provide practical information concerning the use of rivaroxaban for stroke prevention in AF. PMID:25083135