Integration of intracardiac echocardiography and computed tomography during atrial fibrillation ablation: Combining ultrasound contours obtained from the right atrium and ventricular outflow tract.

PubMed

Nakamura, Kohki; Naito, Shigeto; Kaseno, Kenichi; Nakatani, Yosuke; Sasaki, Takehito; Anjo, Naofumi; Yamashita, Eiji; Kumagai, Koji; Funabashi, Nobusada; Kobayashi, Yoshio; Oshima, Shigeru

2017-02-01

We aimed to optimize the acquisition of the left atrial (LA) and pulmonary vein (PV) ultrasound contours for more accurate integration of intracardiac echocardiography (ICE) and computed tomography (CT) using the CARTO ® 3 system during atrial fibrillation (AF) ablation. Eighty-five AF patients underwent integration of ICE and CT using (1) the LA roof and posterior wall contours acquired from the right atrium (RA), (2) all LA/PV contours from the RA (Whole-RA-integration), (3) the LA roof/posterior wall contours from the RA and right ventricular outflow tract (RVOT) (Posterior-RA/RV-integration), and (4) all LA/PV contours from the RA and RVOT (Whole-RA/RV-integration). The integration accuracy was compared using the (1) surface registration error, (2) distances between the three-dimensional CT and eight specific sites on the anterior, posterior, superior, and inferior aspects of the right and left circumferential PV isolation lines, and (3) registration score: a score of 0 or 1 was assigned for whether or not each specific site was visually aligned with the CT, and summed for each method (0 best, 8 worst). Posterior-RA/RV-integration revealed a significantly lower surface registration error (1.30±0.15mm) than Whole-RA- and Whole-RA/RV-integration (p<0.001). The mean distances of the eight specific sites and the registration score for Posterior-RA/RV-integration (median 1.26mm and 2, respectively) were significantly smaller than those for the other integration approaches (p<0.001). Image integration with the LA roof and posterior wall contours acquired from the RA and RVOT may provide greater accuracy for catheter navigation with three-dimensional CT during AF ablation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessment for Learning as Support for Student Self-Regulation

ERIC Educational Resources Information Center

Heritage, Margaret

2018-01-01

Assessment for learning (AfL) is integral to teaching and learning, and has as its central foci (i) pedagogical intervention in the immediacy of student learning, and (ii) the students' agency in the learning and assessment process. The role that students adopt in AfL is consistent with the idea of self-regulated learning, which involves students…

Quality of life, activity impairment, and healthcare resource utilization associated with atrial fibrillation in the US National Health and Wellness Survey.

PubMed

Goren, Amir; Liu, Xianchen; Gupta, Shaloo; Simon, Teresa A; Phatak, Hemant

2013-01-01

This study builds upon current studies of atrial fibrillation (AF) and health outcomes by examining more comprehensively the humanistic burden of illness (quality of life, activity impairment, and healthcare resource utilization) among adult patients with AF, using a large, nationally representative sample and matched controls. Data were analyzed from the Internet-based 2009 US National Health and Wellness Survey. Outcomes were Mental and Physical Component Summary (MCS and PCS) and health utility scores from the SF-12, activity impairment, hospitalizations, and healthcare provider and emergency room (ER) visits. Patients with self-reported diagnosis of AF were matched randomly on age and gender with an equal number of respondents without AF. Generalized linear models examined outcomes as a function of AF vs. non-AF status, controlling for CHADS2 score, comorbidity counts, demographics, and clinical variables. Exploratory structural equation modeling assessed the above in an integrated model of humanistic burden. Mean age of AF patients (1,296 from a total sample of 75,000) was 64.9 years and 65.1% were male. Adjusting for covariates, compared with non-AF patients, AF patients had lower MCS, PCS, and utility scores, greater activity impairment (rate ratio = 1.26), more traditional provider visits (rate ratio = 1.43), and increased odds of ER visits (OR = 2.53) and hospitalizations (OR = 2.71). Exploratory structural equation modeling analyses revealed that persons with AF experienced a significantly higher overall humanistic burden. This study highlights and clarifies the substantial burden of AF and its implications for preparing efficacious AF management plans to address the imminent rise in prevalence.

Words are not enough: nonword repetition as an indicator of arcuate fasciculus integrity during brain tumor resection.

PubMed

Sierpowska, Joanna; Gabarrós, Andreu; Fernandez-Coello, Alejandro; Camins, Àngels; Castañer, Sara; Juncadella, Montserrat; Morís, Joaquín; Rodríguez-Fornells, Antoni

2017-02-01

OBJECTIVE Subcortical electrical stimulation during brain surgery may allow localization of functionally crucial white matter fibers and thus tailoring of the tumor resection according to its functional limits. The arcuate fasciculus (AF) is a white matter bundle connecting frontal, temporal, and parietal cortical areas that is often disrupted by left brain lesions. It plays a critical role in several cognitive functions related to phonological processing, but current intraoperative monitoring methods do not yet allow mapping of this tract with sufficient precision. In the present study the authors aimed to test a new paradigm for the intraoperative monitoring of the AF. METHODS In this report, the authors studied 12 patients undergoing awake brain surgery for tumor resection with a related risk of AF damage. To preserve AF integrity and the cognitive processes sustained by this tract in the intraoperative context, the authors used real word repetition (WR) and nonword repetition (NWR) tasks as complements to standard picture naming. RESULTS Compared with the errors identified by WR or picture naming, the NWR task allowed the detection of subtle errors possibly related to AF alterations. Moreover, only 3 patients demonstrated phonological paraphasias in standard picture naming, and in 2 of these patients the paraphasias co-occurred with the total loss of WR and NWR ability. Before surgery, lesion volume predicted a patient's NWR performance. CONCLUSIONS The authors suggest that monitoring NWR intraoperatively may complement the standard naming tasks and could permit better preservation of the important language production functions subserved by the AF.

Effectiveness of atrial fibrillation rotor ablation is dependent on conduction velocity: An in-silico 3-dimensional modeling study

PubMed Central

Lim, Byounghyun; Hwang, Minki; Song, Jun-Seop; Ryu, Ah-Jin; Joung, Boyoung; Shim, Eun Bo; Ryu, Hyungon

2017-01-01

Background We previously reported that stable rotors are observed in in-silico human atrial fibrillation (AF) models, and are well represented by a dominant frequency (DF). In the current study, we hypothesized that the outcome of DF ablation is affected by conduction velocity (CV) conditions and examined this hypothesis using in-silico 3D-AF modeling. Methods We integrated 3D CT images of left atrium obtained from 10 patients with persistent AF (80% male, 61.8±13.5 years old) into in-silico AF model. We compared AF maintenance durations (max 300s), spatiotemporal stabilities of DF, phase singularity (PS) number, life-span of PS, and AF termination or defragmentation rates after virtual DF ablation with 5 different CV conditions (0.2, 0.3, 0.4, 0.5, and 0.6m/s). Results 1. AF maintenance duration (p<0.001), spatiotemporal mean variance of DF (p<0.001), and the number of PS (p = 0.023) showed CV dependent bimodal patterns (highest at CV0.4m/s and lowest at CV0.6m/s) consistently. 2. After 10% highest DF ablation, AF defragmentation rates were the lowest at CV0.4m/s (37.8%), but highest at CV0.5 and 0.6m/s (all 100%, p<0.001). 3. In the episodes with AF termination or defragmentation followed by 10% highest DF ablation, baseline AF maintenance duration was shorter (p<0.001), spatiotemporal mean variance of DF was lower (p = 0.014), and the number of PS was lower (p = 0.004) than those with failed AF defragmentation after DF ablation. Conclusion Virtual ablation of DF, which may indicate AF driver, was more likely to terminate or defragment AF with spatiotemporally stable DF, but not likely to do so in long-lasting and sustained AF conditions, depending on CV. PMID:29287119

Chassis integrated control for active suspension, active front steering and direct yaw moment systems using hierarchical strategy

NASA Astrophysics Data System (ADS)

Zhao, Jing; Wong, Pak Kin; Ma, Xinbo; Xie, Zhengchao

2017-01-01

This paper proposes a novel integrated controller with three-layer hierarchical structure to coordinate the interactions among active suspension system (ASS), active front steering (AFS) and direct yaw moment control (DYC). First of all, a 14-degree-of-freedom nonlinear vehicle dynamic model is constructed. Then, an upper layer is designed to calculate the total corrected moment for ASS and intermediate layer based on linear moment distribution. By considering the working regions of the AFS and DYC, the intermediate layer is functionalised to determine the trigger signal for the lower layer with corresponding weights. The lower layer is utilised to separately trace the desired value of each local controller and achieve the local control objectives of each subsystem. Simulation results show that the proposed three-layer hierarchical structure is effective in handling the working region of the AFS and DYC, while the quasi-experimental result shows that the proposed integrated controller is able to improve the lateral and vertical dynamics of the vehicle effectively as compared with a conventional electronic stability controller.

Development of a shared decision-making tool to assist patients and clinicians with decisions on oral anticoagulant treatment for atrial fibrillation.

PubMed

Kaiser, Karen; Cheng, Wendy Y; Jensen, Sally; Clayman, Marla L; Thappa, Andrew; Schwiep, Frances; Chawla, Anita; Goldberger, Jeffrey J; Col, Nananda; Schein, Jeff

2015-12-01

Decision aids (DAs) are increasingly used to operationalize shared decision-making (SDM) but their development is not often described. Decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) involve a trade-off between lowering stroke risk and increasing OAC-associated bleeding risk, and consideration of how treatment affects lifestyle. The benefits and risks of OACs hinge upon a patient's risk factors for stroke and bleeding and how they value these outcomes. We present the development of a DA about AF that estimates patients' risks for stroke and bleeding and assesses their preferences for outcomes. Based on a literature review and expert discussions, we identified stroke and major bleeding risk prediction models and embedded them into risk assessment modules. We identified the most important factors in choosing OAC treatment (warfarin used as the default reference OAC) through focus group discussions with AF patients who had used warfarin and clinician interviews. We then designed preference assessment and introductory modules accordingly. We integrated these modules into a prototype AF SDM tool and evaluated its usability through interviews. Our tool included four modules: (1) introduction to AF and OAC treatment risks and benefits; (2) stroke risk assessment; (3) bleeding risk assessment; and (4) preference assessment. Interactive risk calculators estimated patient-specific stroke and bleeding risks; graphics were developed to communicate these risks. After cognitive interviews, the content was improved. The final AF tool calculates patient-specific risks and benefits of OAC treatment and couples these estimates with patient preferences to improve clinical decision-making. The AF SDM tool may help patients choose whether OAC treatment is best for them and represents a patient-centered, integrative approach to educate patients on the benefits and risks of OAC treatment. Future research is needed to evaluate this tool in a real-world setting. The development process presented can be applied to similar SDM tools.

"It's the Other Assessment That Is the Key": Three Norwegian Physical Education Teachers' Engagement (or Not) with Assessment for Learning

ERIC Educational Resources Information Center

Leirhaug, Petter E.; MacPhail, Ann

2015-01-01

The international agenda for assessment continues to convey a growing interest in assessment for learning (AfL) as a tool to support learning and enhance teaching. Complementing this, the recent literature on assessment in physical education acknowledges the need for physical educators to integrate AfL into their teaching and assessment practice…

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus

PubMed Central

van den Akker, Guus G. H.; Surtel, Don A. M.; Cremers, Andy; Richardson, Stephen M.; Hoyland, Judith A.; van Rhijn, Lodewijk W.

2016-01-01

Introduction Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Methods Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). Results The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. Conclusion We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair. PMID:26794306

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus.

PubMed

van den Akker, Guus G H; Surtel, Don A M; Cremers, Andy; Richardson, Stephen M; Hoyland, Judith A; van Rhijn, Lodewijk W; Voncken, Jan Willem; Welting, Tim J M

2016-01-01

Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair.

Human amniotic fluid mesenchymal stem cells in combination with hyperbaric oxygen augment peripheral nerve regeneration.

PubMed

Pan, Hung-Chuan; Chin, Chun-Shih; Yang, Dar-Yu; Ho, Shu-Peng; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou

2009-07-01

Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.

The New 2016 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines: Enough Guidance? Enough Evidence?

PubMed

Castellá, Manuel

2018-04-01

For the first time, the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery have joined forces to develop consensus guidelines for the management of atrial fibrillation (AF). One of the main issues is the integrated care of patients with AF, with emphasis on multidisciplinary teams of general physicians, cardiologists, stroke specialists and surgeons, together with the patient's involvement for better management of AF. These guidelines also help in the detection of risk factors and concomitant cardiovascular diseases, stroke prevention therapies, including anticoagulation and antiplatelet therapies after acute coronary episodes, major haemorrhages or strokes. In the field of ablation, surgery plays an important role as concomitant with other surgical procedures, and it should be considered in symptomatic patients with the highest level of evidence. Asymptomatic patients with mitral insufficiency should also be considered for combined mitral and AF surgery if they have new-onset AF. In patients with stand-alone AF, recommendations for minimally invasive ablation have an increased level of recommendation and should be considered as the same level as catheter ablation in patients with persistent or long-standing persistent AF or with paroxysmal AF who fail catheter ablation. Surgical occlusion or exclusion of the left atrial appendage may be considered for stroke prevention in patients with AF about to have surgery. Nevertheless, not enough is known to avoid long-term anticoagulation in patients at risk of stroke even if the left atrial appendage has been excluded. These Guidelines provide a full spectrum of recommendations on the management of patients with AF including prevention, treatment and complications based on the latest published evidence.

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.

Acute effects of muscle vibration on sensorimotor integration.

PubMed

Lapole, Thomas; Tindel, Jérémy

2015-02-05

Projections from the somesthetic cortex are believed to be involved in the modulation of motor cortical excitability by muscle vibration. The aim of the present pilot study was to analyse the effects of a vibration intervention on short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and afferent facilitation (AF), three intracortical mechanisms reflecting sensorimotor integration. Abductor pollicis brevis (APB) SAI, AF and LAI were investigated on 10 subjects by conditioning test transcranial magnetic stimulation pulses with median nerve electrical stimulation at inter-stimuli intervals in the range 15-25 ms, 25-60 ms, and 100-200 ms, respectively. Test motor evoked potentials (MEPs) were compared to unconditioned MEPs. Measurements were performed before and just after 15 min of vibration applied to the muscle belly of APB at a frequency of 80 Hz. SAI and LAI responses were significantly reduced compared to unconditioned test MEPs (P=0.039 and P<0.001, respectively). AF MEP amplitude was greater than SAI and LAI one (P=0.009 and P=0.004, respectively), but not different from test MEP (P=0.511). There was no significant main effect of vibration (P=0.905). However, 4 subjects were clearly identified as responders. Their mean vibration-induced increase was 324 ± 195% in APB SAI MEP amplitude, and 158 ± 53% and 319 ± 80% in AF and LAI, respectively. Significant differences in SAI, AF and LAI vibration-induced changes were found for responders when compared to non-responders (P=0.019, P=0.038, and P=0.01, respectively). A single session of APB vibration may increase sensorimotor integration, via decreased inhibition and increased facilitation. However, such results were not observed for all subjects, suggesting that other factors (such as attention to the sensory inputs) may have played a role. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A Missense Variant in PLEC Increases Risk of Atrial Fibrillation.

PubMed

Thorolfsdottir, Rosa B; Sveinbjornsson, Gardar; Sulem, Patrick; Helgadottir, Anna; Gretarsdottir, Solveig; Benonisdottir, Stefania; Magnusdottir, Audur; Davidsson, Olafur B; Rajamani, Sridharan; Roden, Dan M; Darbar, Dawood; Pedersen, Terje R; Sabatine, Marc S; Jonsdottir, Ingileif; Arnar, David O; Thorsteinsdottir, Unnur; Gudbjartsson, Daniel F; Holm, Hilma; Stefansson, Kari

2017-10-24

Genome-wide association studies (GWAS) have yielded variants at >30 loci that associate with atrial fibrillation (AF), including rare coding mutations in the sarcomere genes MYH6 and MYL4. The aim of this study was to search for novel AF associations and in doing so gain insights into the mechanisms whereby variants affect AF risk, using electrocardiogram (ECG) measurements. The authors performed a GWAS of 14,255 AF cases and 374,939 controls, using whole-genome sequence data from the Icelandic population, and tested novel signals in 2,002 non-Icelandic cases and 12,324 controls. They then tested the AF variants for effect on cardiac electrical function by using measurements in 289,297 ECGs from 62,974 individuals. The authors discovered 2 novel AF variants, the intergenic variant rs72700114, between the genes LINC01142 and METTL11B (risk allele frequency = 8.1%; odds ratio [OR]: 1.26; p = 3.1 × 10 -18 ), and the missense variant p.Gly4098Ser in PLEC (frequency = 1.2%; OR: 1.55; p = 8.0 × 10 -10 ), encoding plectin, a cytoskeletal cross-linking protein that contributes to integrity of cardiac tissue. The authors also confirmed 29 reported variants. p.Gly4098Ser in PLEC significantly affects various ECG measurements in the absence of AF. Other AF variants have diverse effects on the conduction system, ranging from none to extensive. The discovery of a missense variant in PLEC affecting AF combined with recent discoveries of variants in the sarcomere genes MYH6 and MYL4 points to an important role of myocardial structure in the pathogenesis of the disease. The diverse associations between AF variants and ECG measurements suggest fundamentally different categories of mechanisms contributing to the development of AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Fibrin-Genipin Adhesive Hydrogel for Annulus Fibrosus Repair: Performance Evaluation with Large Animal Organ Culture, In Situ Biomechanics, and In Vivo Degradation Tests

PubMed Central

Likhitpanichkul, M.; Dreischarf, M.; Illien-Junger, S.; Walter, B. A.; Nukaga, T.; Long, R. G; Sakai, D.; Hecht, A. C.; Iatridis, J. C.

2015-01-01

Annulus fibrosus (AF) defects from annular tears, herniation, and discectomy procedures are associated with painful conditions and accelerated intervertebral disc (IVD) degeneration. Currently, no effective treatments exist to repair AF damage, restore IVD biomechanics and promote tissue regeneration. An injectable fibrin-genipin adhesive hydrogel (Fib-Gen) was evaluated for its performance repairing large AF defects in a bovine caudal IVD model using ex vivo organ culture and biomechanical testing of motion segments, and for its in vivo longevity and biocompatibility in a rat model by subcutaneous implantation. Fib-Gen sealed AF defects, prevented IVD height loss, and remained well-integrated with native AF tissue following approximately 14,000 cycles of compression in 6-day organ culture experiments. Fib-Gen repair also retained high viability of native AF cells near the repair site, reduced nitric oxide released to the media, and showed evidence of AF cell migration into the gel. Biomechanically, Fib-Gen fully restored compressive stiffness to intact levels validating organ culture findings. However, only partial restoration of tensile and torsional stiffness was obtained, suggesting opportunities to enhance this formulation. Subcutaneous implantation results, when compared with the literature, suggested Fib-Gen exhibited similar biocompatibility behaviour to fibrin alone but degraded much more slowly. We conclude that injectable Fib-Gen successfully sealed large AF defects, promoted functional restoration with improved motion segment biomechanics, and served as a biocompatible adhesive biomaterial that had greatly enhanced in vivo longevity compared to fibrin. Fib-Gen offers promise for AF repairs that may prevent painful conditions and accelerated degeneration of the IVD, and warrants further material development and evaluation. PMID:25036053

Fibrin-genipin adhesive hydrogel for annulus fibrosus repair: performance evaluation with large animal organ culture, in situ biomechanics, and in vivo degradation tests.

PubMed

Likhitpanichkul, M; Dreischarf, M; Illien-Junger, S; Walter, B A; Nukaga, T; Long, R G; Sakai, D; Hecht, A C; Iatridis, J C

2014-07-18

Annulus fibrosus (AF) defects from annular tears, herniation, and discectomy procedures are associated with painful conditions and accelerated intervertebral disc (IVD) degeneration. Currently, no effective treatments exist to repair AF damage, restore IVD biomechanics and promote tissue regeneration. An injectable fibrin-genipin adhesive hydrogel (Fib-Gen) was evaluated for its performance repairing large AF defects in a bovine caudal IVD model using ex vivo organ culture and biomechanical testing of motion segments, and for its in vivo longevity and biocompatibility in a rat model by subcutaneous implantation. Fib-Gen sealed AF defects, prevented IVD height loss, and remained well-integrated with native AF tissue following approximately 14,000 cycles of compression in 6-day organ culture experiments. Fib-Gen repair also retained high viability of native AF cells near the repair site, reduced nitric oxide released to the media, and showed evidence of AF cell migration into the gel. Biomechanically, Fib-Gen fully restored compressive stiffness to intact levels validating organ culture findings. However, only partial restoration of tensile and torsional stiffness was obtained, suggesting opportunities to enhance this formulation. Subcutaneous implantation results, when compared with the literature, suggested Fib-Gen exhibited similar biocompatibility behaviour to fibrin alone but degraded much more slowly. We conclude that injectable Fib-Gen successfully sealed large AF defects, promoted functional restoration with improved motion segment biomechanics, and served as a biocompatible adhesive biomaterial that had greatly enhanced in vivo longevity compared to fibrin. Fib-Gen offers promise for AF repairs that may prevent painful conditions and accelerated degeneration of the IVD, and warrants further material development and evaluation.

Anticoagulant use for prevention of stroke in a commercial population with atrial fibrillation.

PubMed

Patel, Aarti A; Lennert, Barb; Macomson, Brian; Nelson, Winnie W; Owens, Gary M; Mody, Samir H; Schein, Jeff

2012-07-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF are at an increased risk for stroke. Thromboprophylaxis with vitamin K antagonists reduces the annual incidence of stroke by approximately 60%, but appropriate thromboprophylaxis is prescribed for only approximately 50% of eligible patients. Health plans may help to improve quality of care for patients with AF by analyzing claims data for care improvement opportunities. To analyze pharmacy and medical claims data from a large integrated commercial database to determine the risk for stroke and the appropriateness of anticoagulant use based on guideline recommendations for patients with AF. This descriptive, retrospective claims data analysis used the Anticoagulant Quality Improvement Analyzer software, which was designed to analyze health plan data. The data for this study were obtained from a 10% randomly selected sample from the PharMetrics Integrated Database. This 10% sample resulted in almost 26,000 patients with AF who met the inclusion criteria for this study. Patients with a new or existing diagnosis of AF between July 2008 and June 2010 who were aged ≥18 years were included in this analysis. The follow-up period was 1 year. Demographics, stroke risk level (CHADS2 and CHA2DS2-VASc scores), anticoagulant use, and inpatient stroke hospitalizations were analyzed through the analyzer software. Of the 25,710 patients with AF (CHADS2 score 0-6) who were eligible to be included in this study, 9093 (35%) received vitamin K antagonists and 16,617 (65%) did not receive any anticoagulant. Of the patients at high risk for stroke, as predicted by CHADS2, 39% received an anticoagulant medication. The rates of patients receiving anticoagulant medication varied by age-group-16% of patients aged <65 years, 22% of those aged 65 to 74 years, and 61% of elderly ≥75 years. Among patients hospitalized for stroke, only 28% were treated with an anticoagulant agent in the outpatient setting before admission. Our findings support the current literature, indicating that many patients with AF are not receiving appropriate thromboprophylaxis to counter their risk for stroke. Increased use of appropriate anticoagulation, particularly in high-risk patients, has the potential to reduce the incidence of stroke along with associated fatalities and morbidities.

Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds

PubMed Central

Skardal, Aleksander; Mack, David; Kapetanovic, Edi; Atala, Anthony; Jackson, John D.; Yoo, James

2012-01-01

Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelialization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS cells and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together, our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns. PMID:23197691

Microbial Electrosynthesis and Anaerobic Fermentation: An Economic Evaluation for Acetic Acid Production from CO2 and CO.

PubMed

Christodoulou, Xenia; Velasquez-Orta, Sharon B

2016-10-18

Microbial electrosynthesis (MES) and anaerobic fermentation (AF) are two biological processes capable of reducing CO 2 , CO, and water into acetic acid, an essential industrial reagent. In this study, we evaluated investment and production costs of acetic acid via MES and AF, and compared them to industrial chemical processes: methanol carbonylation and ethane direct oxidation. Production and investment costs were found high-priced for MES (1.44 £/kg, 1770 £/t) and AF (4.14 £/kg, 1598 £/t) because of variable and fixed costs and low production yields (100 t/y) compared to methanol carbonylation (0.26 £/kg, 261 £/t) and ethane direct oxidation (0.11 £/kg, 258 £/t). However, integrating AF with MES would reduce the release of CO 2 , double production rates (200 t/y), and decrease investment costs by 9% (1366 £/t). This resulted into setting the production costs at 0.24 £/kg which is currently market competitive (0.48 £/kg). This economically feasible bioprocess produced molar flow rates of 4550 mol per day from MES and AF independently. Our findings offer a bright opportunity toward the use and scale-up of MES and AF for an economically viable acetic acid production process.

Characterization, stability and in-vivo distribution of asialofetuin glycopeptide incorporating DSPC/CHOL liposomes prepared by mild cholate incubation.

PubMed

Kallinteri, P; Liao, W Y; Antimisiaris, S G; Hwang, K H

2001-04-01

In this study, a small triantennary asialoglycopeptide of fetuin (A-F2) was used as a ligand to direct liposomes to hepatocytes. A-F2 was cleaved from asialofetuin, purified, conjugated with fatty acids and incorporated into pre-formed sonicated DSPC/Chol (2:1) liposomes. A mild cholate incubation method for incorporating the A-F2 ligand on pre-formed vesicles was used. In preliminary in vivo experiments 111In3+ encapsulated in A-F2/palmityl liposomes was seen to accumulate in the liver of mice significantly faster than when encapsulated in non-ligand bearing liposomes of the same lipid composition (studied before), justifying further investigation of this system. The presence of the A-F2/fatty acid conjugate in a functional form on the vesicle surface was confirmed by their reversible agglutination in the presence of Ricinus communis agglutinin (RCA120). Effects of ligand incorporation on the vesicle size distribution, z-potential, membrane integrity and stability were monitored. The results demonstrate that highest ligand incorporation was achieved when liposomes and ligand were co-incubated in the presence of 1 mM sodium cholate. Incorporation increased with the length of the fatty acid used for A-F2 conjugation. Ligand-bearing liposomes were demonstrated to be smaller in diameter (about 30%) with a more positive z-potential in comparison to control vesicles while ligand incorporation did not influence the liposome membrane integrity. The size of the ligand-incorporating vesicles was maintained after 24 hours of incubation in isotonic buffer, proving that the vesicles do not aggregate. Although the preliminary biodistribution results may suggest that ligand bearing liposomes are accumulating in the liver, further cell culture, in vivo distribution and especially liver fractionation studies are required in order to clarify the intrahepatic localization of these liposomes and the ability to target liver hepatocytes in vivo.

Physicochemical characterization of titanium dioxide pigments using various techniques for size determination and asymmetric flow field flow fractionation hyphenated with inductively coupled plasma mass spectrometry.

PubMed

Helsper, Johannes P F G; Peters, Ruud J B; van Bemmel, Margaretha E M; Rivera, Zahira E Herrera; Wagner, Stephan; von der Kammer, Frank; Tromp, Peter C; Hofmann, Thilo; Weigel, Stefan

2016-09-01

Seven commercial titanium dioxide pigments and two other well-defined TiO2 materials (TiMs) were physicochemically characterised using asymmetric flow field flow fractionation (aF4) for separation, various techniques to determine size distribution and inductively coupled plasma mass spectrometry (ICPMS) for chemical characterization. The aF4-ICPMS conditions were optimised and validated for linearity, limit of detection, recovery, repeatability and reproducibility, all indicating good performance. Multi-element detection with aF4-ICPMS showed that some commercial pigments contained zirconium co-eluting with titanium in aF4. The other two TiMs, NM103 and NM104, contained aluminium as integral part of the titanium peak eluting in aF4. The materials were characterised using various size determination techniques: retention time in aF4, aF4 hyphenated with multi-angle laser light spectrometry (MALS), single particle ICPMS (spICPMS), scanning electron microscopy (SEM) and particle tracking analysis (PTA). PTA appeared inappropriate. For the other techniques, size distribution patterns were quite similar, i.e. high polydispersity with diameters from 20 to >700 nm, a modal peak between 200 and 500 nm and a shoulder at 600 nm. Number-based size distribution techniques as spICPMS and SEM showed smaller modal diameters than aF4-UV, from which mass-based diameters are calculated. With aF4-MALS calculated, light-scattering-based "diameters of gyration" (Øg) are similar to hydrodynamic diameters (Øh) from aF4-UV analyses and diameters observed with SEM, but much larger than with spICPMS. A Øg/Øh ratio of about 1 indicates that the TiMs are oblate spheres or fractal aggregates. SEM observations confirm the latter structure. The rationale for differences in modal peak diameter is discussed.

Predictive model for the growth kinetics of Staphylococcus aureus in raw pork developed using Integrated Pathogen Modeling Program (IPMP) 2013.

PubMed

Lee, Yong Ju; Jung, Byeong Su; Kim, Kee-Tae; Paik, Hyun-Dong

2015-09-01

A predictive model was performed to describe the growth of Staphylococcus aureus in raw pork by using Integrated Pathogen Modeling Program 2013 and a polynomial model as a secondary predictive model. S. aureus requires approximately 180 h to reach 5-6 log CFU/g at 10 °C. At 15 °C and 25 °C, approximately 48 and 20 h, respectively, are required to cause food poisoning. Predicted data using the Gompertz model was the most accurate in this study. For lag time (LT) model, bias factor (Bf) and accuracy factor (Af) values were both 1.014, showing that the predictions were within a reliable range. For specific growth rate (SGR) model, Bf and Af were 1.188 and 1.190, respectively. Additionally, both Bf and Af values of the LT and SGR models were close to 1, indicating that IPMP Gompertz model is more adequate for predicting the growth of S. aureus on raw pork than other models. Copyright © 2015 Elsevier Ltd. 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 diagnostic codes for identification of AF and suspected adverse events is a source of potential investigator error. A direct cause-effect relationship between suspected adverse events/function tests and AF therapy cannot be confirmed based on the claims data available. The incidence of suspected adverse events and adverse event monitoring during AF rhythm-control and/or rate-control therapy is high. Costs associated with adverse events and adverse event monitoring are likely to add considerably to the overall burden of AF management.

Amniotic fluid stem cells rescue both in vitro and in vivo growth, innervation, and motility in nitrofen-exposed hypoplastic rat lungs through paracrine effects.

PubMed

Pederiva, F; Ghionzoli, M; Pierro, A; De Coppi, P; Tovar, J A

2013-01-01

Lung hypoplasia can be prevented in vitro by retinoic acid (RA). Recent evidence suggests that amniotic fluid stem (AFS) cells may integrate injured lungs and influence their recovery. We tested the hypothesis that AFS cells might improve lung growth and motility by paracrine mechanisms. Pregnant rats received either nitrofen or vehicle on E9.5. In vitro E13 embryonic lungs were cultured in the presence of culture medium alone or with RA, basophils, or AFS cells. In vivo green fluorescent protein-expressing (GFP(+)) rat AFS cells were transplanted in nitrofen-exposed rats on E10.5. E13 lung explants were cultured before analysis. The surface, the number of terminal buds, and the frequency of bronchial contractions were assessed. Protein gene product 9.5 (PGP 9.5) and α-actin protein levels were measured. The lung explants transplanted with AFS cells were stained for α-actin, PGP 9.5, and TTF-1. The levels of FGF-10, VEGFα, and TGF-β1 secreted by the AFS cells in the culture medium were measured. Comparison between groups was made by ANOVA. In vitro, the surface, the number of terminal buds, and the bronchial peristalsis were increased in nitrofen+AFS cell explants in comparison with nitrofen-exposed lungs. While nitrofen+RA lungs were similar to nitrofen+AFS ones, basophils did not normalize these measurements. PGP 9.5 protein was decreased in nitrofen lungs, but after adding AFS cells, the value was similar to controls. No differences were found in the expression of α-actin. In vivo, the surface, number of terminal buds, and peristalsis were similar to control after injection of AFS cells in nitrofen-exposed rats. Colocalization with TTF-1-positive cells was found. The levels of FGF-10 and VEGFα were increased in nitrofen+AFS cell explants, while the levels of TGF-β1 were similar to controls. Lung growth, bronchial motility, and innervation were decreased in nitrofen explants and rescued by AFS cells both in vitro and in vivo, similarly to that observed before with RA. The AFS cell beneficial effect was probably related to paracrine action of growth factor secretion.

Angle-ply biomaterial scaffold for annulus fibrosus repair replicates native tissue mechanical properties, restores spinal kinematics, and supports cell viability.

PubMed

Borem, Ryan; Madeline, Allison; Walters, Joshua; Mayo, Henry; Gill, Sanjitpal; Mercuri, Jeremy

2017-08-01

Annulus fibrosus (AF) damage commonly occurs due to intervertebral disc (IVD) degeneration/herniation. The dynamic mechanical role of the AF is essential for proper IVD function and thus it is imperative that biomaterials developed to repair the AF withstand the mechanical rigors of the native tissue. Furthermore, these biomaterials must resist accelerated degradation within the proteolytic environment of degenerate IVDs while supporting integration with host tissue. We have previously reported a novel approach for developing collagen-based, multi-laminate AF repair patches (AFRPs) that mimic the angle-ply architecture and basic tensile properties of the human AF. Herein, we further evaluate AFRPs for their: tensile fatigue and impact burst strength, IVD attachment strength, and contribution to functional spinal unit (FSU) kinematics following IVD repair. Additionally, AFRP resistance to collagenase degradation and cytocompatibility were assessed following chemical crosslinking. In summary, AFRPs demonstrated enhanced durability at high applied stress amplitudes compared to human AF and withstood radially-directed biaxial stresses commonly borne by the native tissue prior to failure/detachment from IVDs. Moreover, FSUs repaired with AFRPs and nucleus pulposus (NP) surrogates had their axial kinematic parameters restored to intact levels. Finally, carbodiimide crosslinked AFRPs resisted accelerated collagenase digestion without detrimentally effecting AFRP tensile properties or cytocompatibility. Taken together, AFRPs demonstrate the mechanical robustness and enzymatic stability required for implantation into the damaged/degenerate IVD while supporting AF cell infiltration and viability. The quality of life for millions of individuals globally is detrimentally impacted by IVD degeneration and herniation. These pathologies often result in the structural demise of IVD tissue, particularly the annulus fibrosus (AF). Biomaterials developed for AF repair have yet to demonstrate the mechanical strength and durability required for utilization in the spine. Herein, we demonstrate the development of an angle-ply AF repair patch (AFRP) that can resist the application of physiologically relevant stresses without failure and which contributes to the restoration of functional spinal unit axial kinematics following repair. Furthermore, we show that this biomaterial can resist accelerated degradation in a simulated degenerate environment and supports AF cell viability. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Arctic freshwater synthesis: Introduction

NASA Astrophysics Data System (ADS)

Prowse, T.; Bring, A.; Mârd, J.; Carmack, E.

2015-11-01

In response to a joint request from the World Climate Research Program's Climate and Cryosphere Project, the International Arctic Science Committee, and the Arctic Council's Arctic Monitoring and Assessment Program, an updated scientific assessment has been conducted of the Arctic Freshwater System (AFS), entitled the Arctic Freshwater Synthesis (AFSΣ). The major reason for joint request was an increasing concern that changes to the AFS have produced, and could produce even greater, changes to biogeophysical and socioeconomic systems of special importance to northern residents and also produce extra-Arctic climatic effects that will have global consequences. Hence, the key objective of the AFSΣ was to produce an updated, comprehensive, and integrated review of the structure and function of the entire AFS. The AFSΣ was organized around six key thematic areas: atmosphere, oceans, terrestrial hydrology, terrestrial ecology, resources and modeling, and the review of each coauthored by an international group of scientists and published as separate manuscripts in this special issue of Journal of Geophysical Research-Biogeosciences. This AFSΣ—Introduction reviews the motivations for, and foci of, previous studies of the AFS, discusses criteria used to define the domain of the AFS, and details key characteristics of the definition adopted for the AFSΣ.

Improving Air Force Command and Control Through Enhanced Agile Combat Support Planning, Execution, Monitoring, and Control Processes

DTIC Science & Technology

2012-01-01

Tripp, Lionel A. Galway , Timothy L. Ramey, Mahyar A. Amouzegar, and Eric Peltz (MR-1179-AF), 2000. This report describes a vision for the combat...Postures, Lionel  A. Galway , Robert S. Tripp, Timothy  L. Ramey, and John G. Drew (MR-1075-AF), 2000. This report describes how alternative resourcing of...Aerospace Forces: An Integrated Strate- gic Agile Combat Support Planning Framework, Robert S. Tripp, Lionel  A. Galway , Paul Killingsworth, Eric Peltz

Simple Model for Identifying Critical Regions in Atrial Fibrillation

NASA Astrophysics Data System (ADS)

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

2015-01-01

Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wave front propagation on an anisotropic structure mimicking the branching network of heart muscle cells. This integration of phenomenological dynamics and pertinent structure shows how AF emerges spontaneously when the transverse cell-to-cell coupling decreases, as occurs with age, beyond a threshold value. We identify critical regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia and express the threshold value of transversal cell-to-cell coupling as a function of the model parameters. This threshold value decreases with increasing refractory period by reducing the number of critical regions which can initiate and sustain microreentrant circuits. These biologically testable predictions might inform ablation therapies and arrhythmic risk assessment.

Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

PubMed

Walters, Tomos E; Kalman, Jonathan M; Patel, Sheila K; Mearns, Megan; Velkoska, Elena; Burrell, Louise M

2017-08-01

Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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 East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Trial registration Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. PMID:28729311

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. Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An ultra-low-voltage electronic implementation of inertial neuron model with nonmonotonous Liao's activation function.

PubMed

Kant, Nasir Ali; Dar, Mohamad Rafiq; Khanday, Farooq Ahmad

2015-01-01

The output of every neuron in neural network is specified by the employed activation function (AF) and therefore forms the heart of neural networks. As far as the design of artificial neural networks (ANNs) is concerned, hardware approach is preferred over software one because it promises the full utilization of the application potential of ANNs. Therefore, besides some arithmetic blocks, designing AF in hardware is the most important for designing ANN. While attempting to design the AF in hardware, the designs should be compatible with the modern Very Large Scale Integration (VLSI) design techniques. In this regard, the implemented designs should: only be in Metal Oxide Semiconductor (MOS) technology in order to be compatible with the digital designs, provide electronic tunability feature, and be able to operate at ultra-low voltage. Companding is one of the promising circuit design techniques for achieving these goals. In this paper, 0.5 V design of Liao's AF using sinh-domain technique is introduced. Furthermore, the function is tested by implementing inertial neuron model. The performance of the AF and inertial neuron model have been evaluated through simulation results, using the PSPICE software with the MOS transistor models provided by the 0.18-μm Taiwan Semiconductor Manufacturer Complementary Metal Oxide Semiconductor (TSM CMOS) process.

Anti-arrhythmic strategies for atrial fibrillation

PubMed Central

Grandi, Eleonora; Maleckar, Mary M.

2016-01-01

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with increased risk of cerebrovascular stroke, and with several other pathologies, including heart failure. Current therapies for AF are targeted at reducing risk of stroke (anticoagulation) and tachycardia-induced cardiomyopathy (rate or rhythm control). Rate control, typically achieved by atrioventricular nodal blocking drugs, is often insufficient to alleviate symptoms. Rhythm control approaches include antiarrhythmic drugs, electrical cardioversion, and ablation strategies. Here, we offer several examples of how computational modeling can provide a quantitative framework for integrating multi scale data to: (a) gain insight into multi-scale mechanisms of AF; (b) identify and test pharmacological and electrical therapy and interventions; and (c) support clinical decisions. We review how modeling approaches have evolved and contributed to the research pipeline and preclinical development and discuss future directions and challenges in the field. PMID:27612549

Defining disease phenotypes using national linked electronic health records: a case study of atrial fibrillation.

PubMed

Morley, Katherine I; Wallace, Joshua; Denaxas, Spiros C; Hunter, Ross J; Patel, Riyaz S; Perel, Pablo; Shah, Anoop D; Timmis, Adam D; Schilling, Richard J; Hemingway, Harry

2014-01-01

National electronic health records (EHR) are increasingly used for research but identifying disease cases is challenging due to differences in information captured between sources (e.g. primary and secondary care). Our objective was to provide a transparent, reproducible model for integrating these data using atrial fibrillation (AF), a chronic condition diagnosed and managed in multiple ways in different healthcare settings, as a case study. Potentially relevant codes for AF screening, diagnosis, and management were identified in four coding systems: Read (primary care diagnoses and procedures), British National Formulary (BNF; primary care prescriptions), ICD-10 (secondary care diagnoses) and OPCS-4 (secondary care procedures). From these we developed a phenotype algorithm via expert review and analysis of linked EHR data from 1998 to 2010 for a cohort of 2.14 million UK patients aged ≥ 30 years. The cohort was also used to evaluate the phenotype by examining associations between incident AF and known risk factors. The phenotype algorithm incorporated 286 codes: 201 Read, 63 BNF, 18 ICD-10, and four OPCS-4. Incident AF diagnoses were recorded for 72,793 patients, but only 39.6% (N = 28,795) were recorded in primary care and secondary care. An additional 7,468 potential cases were inferred from data on treatment and pre-existing conditions. The proportion of cases identified from each source differed by diagnosis age; inferred diagnoses contributed a greater proportion of younger cases (≤ 60 years), while older patients (≥ 80 years) were mainly diagnosed in SC. Associations of risk factors (hypertension, myocardial infarction, heart failure) with incident AF defined using different EHR sources were comparable in magnitude to those from traditional consented cohorts. A single EHR source is not sufficient to identify all patients, nor will it provide a representative sample. Combining multiple data sources and integrating information on treatment and comorbid conditions can substantially improve case identification.

Arrhythmia Evaluation in Wearable ECG Devices

PubMed Central

Sadrawi, Muammar; Lin, Chien-Hung; Hsieh, Yita; Kuo, Chia-Chun; Chien, Jen Chien; Haraikawa, Koichi; Abbod, Maysam F.; Shieh, Jiann-Shing

2017-01-01

This study evaluates four databases from PhysioNet: The American Heart Association database (AHADB), Creighton University Ventricular Tachyarrhythmia database (CUDB), MIT-BIH Arrhythmia database (MITDB), and MIT-BIH Noise Stress Test database (NSTDB). The ANSI/AAMI EC57:2012 is used for the evaluation of the algorithms for the supraventricular ectopic beat (SVEB), ventricular ectopic beat (VEB), atrial fibrillation (AF), and ventricular fibrillation (VF) via the evaluation of the sensitivity, positive predictivity and false positive rate. Sample entropy, fast Fourier transform (FFT), and multilayer perceptron neural network with backpropagation training algorithm are selected for the integrated detection algorithms. For this study, the result for SVEB has some improvements compared to a previous study that also utilized ANSI/AAMI EC57. In further, VEB sensitivity and positive predictivity gross evaluations have greater than 80%, except for the positive predictivity of the NSTDB database. For AF gross evaluation of MITDB database, the results show very good classification, excluding the episode sensitivity. In advanced, for VF gross evaluation, the episode sensitivity and positive predictivity for the AHADB, MITDB, and CUDB, have greater than 80%, except for MITDB episode positive predictivity, which is 75%. The achieved results show that the proposed integrated SVEB, VEB, AF, and VF detection algorithm has an accurate classification according to ANSI/AAMI EC57:2012. In conclusion, the proposed integrated detection algorithm can achieve good accuracy in comparison with other previous studies. Furthermore, more advanced algorithms and hardware devices should be performed in future for arrhythmia detection and evaluation. PMID:29068369

OCULUS fire: a command and control system for fire management with crowd sourcing and social media interconnectivity

NASA Astrophysics Data System (ADS)

Thomopoulos, Stelios C. A.; Kyriazanos, Dimitris M.; Astyakopoulos, Alkiviadis; Dimitros, Kostantinos; Margonis, Christos; Thanos, Giorgos Konstantinos; Skroumpelou, Katerina

2016-05-01

AF3 (Advanced Forest Fire Fighting2) is a European FP7 research project that intends to improve the efficiency of current fire-fighting operations and the protection of human lives, the environment and property by developing innovative technologies to ensure the integration between existing and new systems. To reach this objective, the AF3 project focuses on innovative active and passive countermeasures, early detection and monitoring, integrated crisis management and advanced public information channels. OCULUS Fire is the innovative control and command system developed within AF3 as a monitoring, GIS and Knowledge Extraction System and Visualization Tool. OCULUS Fire includes (a) an interface for real-time updating and reconstructing of maps to enable rerouting based on estimated hazards and risks, (b) processing of GIS dynamic re-construction and mission re-routing, based on the fusion of airborne, satellite, ground and ancillary geolocation data, (c) visualization components for the C2 monitoring system, displaying and managing information arriving from a variety of sources and (d) mission and situational awareness module for OCULUS Fire ground monitoring system being part of an Integrated Crisis Management Information System for ground and ancillary sensors. OCULUS Fire will also process and visualise information from public information channels, social media and also mobile applications by helpful citizens and volunteers. Social networking, community building and crowdsourcing features will enable a higher reliability and less false alarm rates when using such data in the context of safety and security applications.

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 diagnosis and treatment of this arrhythmia and related consequences.

White Matter Integrity and Treatment-Based Change in Speech Performance in Minimally Verbal Children with Autism Spectrum Disorder.

PubMed

Chenausky, Karen; Kernbach, Julius; Norton, Andrea; Schlaug, Gottfried

2017-01-01

We investigated the relationship between imaging variables for two language/speech-motor tracts and speech fluency variables in 10 minimally verbal (MV) children with autism. Specifically, we tested whether measures of white matter integrity-fractional anisotropy (FA) of the arcuate fasciculus (AF) and frontal aslant tract (FAT)-were related to change in percent syllable-initial consonants correct, percent items responded to, and percent syllable insertion errors (from best baseline to post 25 treatment sessions). Twenty-three MV children with autism spectrum disorder (ASD) received Auditory-Motor Mapping Training (AMMT), an intonation-based treatment to improve fluency in spoken output, and we report on seven who received a matched control treatment. Ten of the AMMT participants were able to undergo a magnetic resonance imaging study at baseline; their performance on baseline speech production measures is compared to that of the other two groups. No baseline differences were found between groups. A canonical correlation analysis (CCA) relating FA values for left- and right-hemisphere AF and FAT to speech production measures showed that FA of the left AF and right FAT were the largest contributors to the synthetic independent imaging-related variable. Change in percent syllable-initial consonants correct and percent syllable-insertion errors were the largest contributors to the synthetic dependent fluency-related variable. Regression analyses showed that FA values in left AF significantly predicted change in percent syllable-initial consonants correct, no FA variables significantly predicted change in percent items responded to, and FA of right FAT significantly predicted change in percent syllable-insertion errors. Results are consistent with previously identified roles for the AF in mediating bidirectional mapping between articulation and acoustics, and the FAT in its relationship to speech initiation and fluency. They further suggest a division of labor between the hemispheres, implicating the left hemisphere in accuracy of speech production and the right hemisphere in fluency in this population. Changes in response rate are interpreted as stemming from factors other than the integrity of these two fiber tracts. This study is the first to document the existence of a subgroup of MV children who experience increases in syllable- insertion errors as their speech develops in response to therapy.

Congruence between the Intended, Implemented, and Attained ICT Curricula in Sub-Saharan Africa

ERIC Educational Resources Information Center

Mereku, Damian Kofi; Mereku, Cosmas Worlanyo Kofi

2015-01-01

The PanAfrican Research Agenda on the Pedagogical Integration of information and communication technology (ICT; PanAf) research project was initiated in 2006 to support initiatives in African countries to integrate ICT into teaching and learning through the frequent collection and analysis of data on ICT usage. The article examines the congruence…

From rhetoric to reality: consumer engagement in 16 multi-stakeholder alliances.

PubMed

Greene, Jessica; Farley, Diane C; Christianson, Jon B; Scanlon, Dennis P; Shi, Yunfeng

2016-08-01

A key component of the Aligning Forces for Quality (AF4Q) program was engaging consumers in their health and healthcare. We examined the extent to which the alliances embraced 4 areas of consumer engagement: self-management, consumer friendliness of reports of healthcare provider quality, involvement of consumers in alliance governance, and the integration of consumers into quality improvement teams. We used a largely qualitative approach. The evaluation team conducted 1100 in-depth interviews with alliance stakeholders. Two authors reviewed the consumer engagement data for each alliance to assess its level of embrace in the 4 consumer engagement areas. For consumer friendliness of public reporting websites, we also assessed alliance public reports for reading level, technical language, and evaluable displays. Population-level effects were also examined for self-management and public reporting. Consumer engagement was new to most alliances, and few had staff with consumer engagement expertise or existing consumer constituencies. For each area of consumer engagement, some alliances enthusiastically embraced the work, other alliances made a concerted but limited effort to develop programs, and a third group of alliances did the minimum work required. Integrating consumers into governance was the area most often embraced, followed by making public reports consumer friendly. Two alliances strongly embraced both self-management and integrating patients into quality improvement efforts. The AF4Q program did not have greater population level effects from self-management or public reporting than were those observed in a national comparison sample. The AF4Q program sparked a few alliances to develop robust consumer engagement programming, while most alliances tried consumer engagement efforts for the first time and developed an appreciation for integrating consumer perspectives into their work.

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction.

PubMed

Beltrami, Matteo; Palazzuoli, Alberto; Padeletti, Luigi; Cerbai, Elisabetta; Coiro, Stefano; Emdin, Michele; Marcucci, Rossella; Morrone, Doralisa; Cameli, Matteo; Savino, Ketty; Pedrinelli, Roberto; Ambrosio, Giuseppe

2018-02-01

Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies. © 2017 John Wiley & Sons Ltd.

Global-scale high-resolution ( 1 km) modelling of mean, maximum and minimum annual streamflow

NASA Astrophysics Data System (ADS)

Barbarossa, Valerio; Huijbregts, Mark; Hendriks, Jan; Beusen, Arthur; Clavreul, Julie; King, Henry; Schipper, Aafke

2017-04-01

Quantifying mean, maximum and minimum annual flow (AF) of rivers at ungauged sites is essential for a number of applications, including assessments of global water supply, ecosystem integrity and water footprints. AF metrics can be quantified with spatially explicit process-based models, which might be overly time-consuming and data-intensive for this purpose, or with empirical regression models that predict AF metrics based on climate and catchment characteristics. Yet, so far, regression models have mostly been developed at a regional scale and the extent to which they can be extrapolated to other regions is not known. We developed global-scale regression models that quantify mean, maximum and minimum AF as function of catchment area and catchment-averaged slope, elevation, and mean, maximum and minimum annual precipitation and air temperature. We then used these models to obtain global 30 arc-seconds (˜ 1 km) maps of mean, maximum and minimum AF for each year from 1960 through 2015, based on a newly developed hydrologically conditioned digital elevation model. We calibrated our regression models based on observations of discharge and catchment characteristics from about 4,000 catchments worldwide, ranging from 100 to 106 km2 in size, and validated them against independent measurements as well as the output of a number of process-based global hydrological models (GHMs). The variance explained by our regression models ranged up to 90% and the performance of the models compared well with the performance of existing GHMs. Yet, our AF maps provide a level of spatial detail that cannot yet be achieved by current GHMs.

Prediction of Functional Overreaching From Subjective Fatigue and Readiness to Train After Only 3 Days of Cycling.

PubMed

Ten Haaf, Twan; van Staveren, Selma; Oudenhoven, Erik; Piacentini, Maria F; Meeusen, Romain; Roelands, Bart; Koenderman, Leo; Daanen, Hein A M; Foster, Carl; de Koning, Jos J

2017-04-01

To investigate whether monitoring of easily measurable stressors and symptoms can be used to distinguish early between acute fatigue (AF) and functional overreaching (FOR). The study included 30 subjects (11 female, 19 male; age 40.8 ± 10.8 y, VO 2 max 51.8 ± 6.3 mL · kg -1 · min -1 ) who participated in an 8-d cycling event over 1300 km with 18,500 climbing meters. Performance was measured before and after the event using a maximal incremental test. Subjects with decreased performance after the event were classified as FOR, others as AF. Mental and physical well-being, internal training load, resting heart rate, temperature, and mood were measured daily during the event. Differences between AF and FOR were analyzed using mixed-model ANOVAs. Logistic regression was used to determine the best predictors of FOR after 3 and 6 d of cycling. Fifteen subjects were classified as FOR and 14 as AF (1 excluded). Although total group changes were observed during the event, no differences between AF and FOR were found for individual monitoring parameters. The combination of questionnaire-based changes in fatigue and readiness to train after 3 d cycling correctly predicted 78% of the subjects as AF or FOR (sensitivity = 79%, specificity = 77%). Monitoring changes in fatigue and readiness to train, using simple visual analog scales, can be used to identify subjects likely to become FOR after only 3 d of cycling. Hence, we encourage athlete support staff to monitor not only fatigue but also the subjective integrated mental and physical readiness to perform.

Disruption of actin filaments in Zea mays by bisphenol A depends on their crosstalk with microtubules.

PubMed

Stavropoulou, Konstantina; Adamakis, Ioannis-Dimosthenis S; Panteris, Emmanuel; Arseni, Ermioni-Makedonia; Eleftheriou, Eleftherios P

2018-03-01

Bisphenol A (BPA) is a widespread environmental pollutant, reportedly harmful to living organisms. In plant cells, BPA was shown to disrupt microtubule (MT) arrays and perturb mitosis, but its effects on filamentous actin (F-actin) have not been explored. Here we studied the effects of BPA on actin filaments (AFs) in meristematic root tip and leaf cells of Zea mays, by fluorescent labeling and confocal microscopy. Considering the typical dynamic interaction between MTs and AFs, the effects on these two essential components of the plant cytoskeleton were correlated. It was found that BPA disorganized rapidly AFs in a concentration- and time-dependent manner. The fine filaments were first to be affected, followed by the subcortical bundles, resulting in rod- and ring-like conformations. The observed differences in sensitivity between protodermal and cortex cells were attributed to the deeper location of the latter. Depolymerization or stabilization of MTs by relevant drugs (oryzalin, taxol) revealed that AF susceptibility to BPA depends on MT integrity. Developing leaves required harder and longer treatment to be affected by BPA. Ontogenesis of stomatal complexes was highly disturbed, arrangement of AFs and MT arrays was disordered and accuracy of cell division sequence was deranged or completely arrested. The effect of BPA confirmed that subsidiary cell mother cell polarization is not mediated by F-actin patch neither of preprophase band organization. On the overall, it is concluded that AFs in plant cells constitute a subcellular target of BPA and their disruption depends on their crosstalk with MTs. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Left, The Better: White-Matter Brain Integrity Predicts Foreign Language Imitation Ability.

PubMed

Vaquero, Lucía; Rodríguez-Fornells, Antoni; Reiterer, Susanne M

2017-08-01

Speech imitation is crucial for language acquisition and second-language learning. Interestingly, large individual differences regarding the ability in imitating foreign-language sounds have been observed. The origin of this interindividual diversity remains unknown, although it might be partially explained by structural predispositions. Here we correlated white-matter structural properties of the arcuate fasciculus (AF) with the performance of 52 German-speakers in a Hindi sentence- and word-imitation task. First, a manual reconstruction was performed, permitting us to extract the mean values along the three branches of the AF. We found that a larger lateralization of the AF volume toward the left hemisphere predicted the performance of our participants in the imitation task. Second, an automatic reconstruction was carried out, allowing us to localize the specific region within the AF that exhibited the largest correlation with foreign language imitation. Results of this reconstruction also showed a left lateralization trend: greater fractional anisotropy values in the anterior half of the left AF correlated with the performance in the Hindi-imitation task. From the best of our knowledge, this is the first time that foreign language imitation aptitude is tested using a more ecological imitation task and correlated with DTI tractography, using both a manual and an automatic method. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Evaluation of the implementation and impact of an integrated prevention model on the academic progress of students with disabilities.

PubMed

Barlow, Alexandra; Humphrey, Neil; Lendrum, Ann; Wigelsworth, Michael; Squires, Garry

2014-11-12

In this paper we report on the implementation and impact of an integrated prevention model (Achievement for All - AfA) to improve the educational experiences and outcomes of students with disabilities. It comprises three inter-related strands: assessment, tracking and intervention; structured conversations with parents; and, developing provision for wider outcomes. Participants were 12,038 students with disabilities from 431 mainstream primary and secondary schools across 10 Local Authorities in England involved in the two-year AfA pilot. Pre- and post-test data on academic attainment in English and Maths were compared with national data on academic progress for students with and without disabilities over an equivalent period of time. School-level contextual and implementation data and student-level socio-demographic and psychosocial data were also collected. Four hypotheses were tested regarding the impact of AfA on academic attainment in English (H1) and Maths (H2); the influence of aspects of the implementation context and processes (H3); and individual differences between students (H4). Our findings are discussed in relation to the identification and validation of critical intervention components and standards for assessing the practical significance of attempts to improve outcomes for students. Copyright © 2014 Elsevier Ltd. All rights reserved.

microRNA regulatory mechanism by which PLLA aligned nanofibers influence PC12 cell differentiation

NASA Astrophysics Data System (ADS)

Yu, Yadong; Lü, Xiaoying; Ding, Fei

2015-08-01

Objective. Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. Approach. Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined. Then, SOLiD sequencing and cDNA microarray were employed to profile the expressions of miRNAs and mRNAs. The target genes of the misregulated miRNAs were predicted and compared with the mRNA profile data. Functions of the matched target genes (the intersection between the predicted target genes and the experimentally-determined, misregulated genes) were analyzed. Main results. The results revealed that neurites spread in various directions in control and RF groups. In the AF group, most neurites extended in parallel with each other. The glucose consumption and lactic acid production in the RF and AF groups were higher than those in the control group. Compared with the control group, 42 and 94 miRNAs were significantly dysregulated in the RF and AF groups, respectively. By comparing the predicted target genes with the mRNA profile data, five and 87 matched target genes were found in the RF and AF groups, respectively. Three of the matched target genes in the AF group were found to be associated with neuronal differentiation, whereas none had this association in the RF group. The PLLA AFs induced the dysregulation of miRNAs that regulate many biological functions, including axonal guidance, lipid metabolism and long-term potentiation. In particular, two miRNA-matched target gene-biological function modules associated with neuronal differentiation were identified as follows: (1) miR-23b, miR-18a, miR-107 and miR-103 regulate the Rras2 and Nf1 gene and thereby, affect cytoskeleton regulation and MAPK pathway; (2) miR-92a, miR-339-5p, miR-25, miR-125a-5p, miR-351 and miR-19b co-regulate the Pafah1b1 gene, affecting PC12 cell migration and differentiation. Significance. This work demonstrates a bioinformatic approach to accomplish miRNA-mRNA profile integrative analysis and provides more insights for understanding the regulatory mechanism of miRNA in AFs affecting neuronal differentiation. These findings will be greatly beneficial for the application and design of AFs in nerve tissue engineering.

Effect of interconnection between cervical vagus trunk, epicardial fat pad on sinus node function, and atrial fibrillation.

PubMed

Zhou, Qina; Zhang, Ling; Wang, Kun; Xu, Xiaoxia; Ji, Meng; Zhang, Feng; Wang, Hongli; Hou, Yuemei

2014-03-01

The epicardial fat pad (FP) integrates the autonomic innervation between the extrinsic and intrinsic cardiac autonomic nervous system and affects atrial electrophysiology and pathophysiology. Eighteen dogs were divided into two groups: sequential ablation of sinoatrial node FP (SAN-FP) and atrioventricular node FP (AVN-FP). Sinus rate (SR), atrial fibrillation (AF) inducibility, and effective refractory period (ERP) changes during electrical stimulation of the vagus trunk were detected before and after ablation. In the SAN-FP group, the SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were significantly attenuated by isolated SAN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent AVN-FP ablation following SAN-FP ablation almost cannot produce further attenuation during vagus trunk stimulation, compared with isolated SAN-FP ablation (P > 0.05). In the AVN-FP group, SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were completely eliminated by isolated AVN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent SAN-FP ablation following AVN-FP ablation produced no further attenuation, compared with isolated AVN-FP ablation (P > 0.05). A neural pathway from the cervical vagus trunk to the sinus node and atrium runs through the SAN-FP, but eventually converges at the AVN-FP and also suggested that the AVN-FP serves as an "integration center" for the SAN-FP to modulate sinus node function. The AVN-FP may play a more critical role in the initiation and maintenance of AF. ©2013 First Affilated Hospital of Xingiang Medical University Pacing and Clinical Electrophysiology ©2013 Wiley Periodicals, Inc.

Lack of Exposure in a First-in-Man Study Due to Aldehyde Oxidase Metabolism: Investigated by Use of 14C-microdose, Humanized Mice, Monkey Pharmacokinetics, and In Vitro Methods.

PubMed

Jensen, Klaus Gjervig; Jacobsen, Anne-Marie; Bundgaard, Christoffer; Nilausen, Dorrit Østergaard; Thale, Zia; Chandrasena, Gamini; Jørgensen, Martin

2017-01-01

Inclusion of a microdose of 14 C-labeled drug in the first-in-man study of new investigational drugs and subsequent analysis by accelerator mass spectrometry has become an integrated part of drug development at Lundbeck. It has been found to be highly informative with regard to investigations of the routes and rates of excretion of the drug and the human metabolite profiles according to metabolites in safety testing guidance and also when additional metabolism-related issues needed to be addressed. In the first-in-man study with the NCE Lu AF09535, contrary to anticipated, surprisingly low exposure was observed when measuring the parent compound using conventional bioanalysis. Parallel accelerator mass spectrometry analysis revealed that the low exposure was almost exclusively attributable to extensive metabolism. The metabolism observed in humans was mediated via a human specific metabolic pathway, whereas an equivalent extent of metabolism was not observed in preclinical species. In vitro, incubation studies in human liver cytosol revealed involvement of aldehyde oxidase (AO) in the biotransformation of Lu AF09535. In vivo, substantially lower plasma exposure of Lu AF09535 was observed in chimeric mice with humanized livers compared with control animals. In addition, Lu AF09535 exhibited very low oral bioavailability in monkeys despite relatively low clearance after intravenous administration in contrast to the pharmacokinetics in rats and dogs, both showing low clearance and high bioavailability. The in vitro and in vivo methods applied were proved useful for identifying and evaluating AO-dependent metabolism. Different strategies to integrate these methods for prediction of in vivo human clearance of AO substrates were evaluated. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

PubMed Central

Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

2014-01-01

Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

Atrial fibrillation ablation using very short duration 50 W ablations and contact force sensing catheters.

PubMed

Winkle, Roger A; Moskovitz, Ryan; Hardwin Mead, R; Engel, Gregory; Kong, Melissa H; Fleming, William; Salcedo, Jonathan; Patrawala, Rob A; Tranter, John H; Shai, Isaac

2018-06-01

The optimal radiofrequency (RF) power and lesion duration using contact force (CF) sensing catheters for atrial fibrillation (AF) ablation are unknown. We evaluate 50 W RF power for very short durations using CF sensing catheters during AF ablation. We evaluated 51 patients with paroxysmal (n = 20) or persistent (n = 31) AF undergoing initial RF ablation. A total of 3961 50 W RF lesions were given (average 77.6 ± 19.1/patient) for an average duration of only 11.2 ± 3.7 s. As CF increased from < 10 to > 40 g, the RF application duration decreased from 13.7 ± 4.4 to 8.6 ± 2.5 s (p < 0.0005). Impedance drops occurred in all ablations, and for patients in sinus rhythm, there was loss of pacing capture during RF delivery suggesting lesion creation. Only 3% of the ablation lesions were at < 5 g and 1% at > 40 g of force. As CF increased, the force time integral (FTI) increased from 47 ± 24 to 376 ± 102 gs (p < 0.0005) and the lesion index (LSI) increased from 4.10 ± 0.51 to 7.63 ± 0.50 (p < 0.0005). Both procedure time (101 ± 19.7 min) and total RF energy time (895 ± 258 s) were very short. For paroxysmal AF, the single procedure freedom from AF was 86% at 1 and 2 years. For persistent AF, it was 83% at 1 year and 72% at 2 years. There were no complications. Short duration 50 W ablations using CF sensing catheters are safe and result in excellent long-term freedom from AF for both paroxysmal and persistent AF with short procedure times and small amounts of total RF energy delivery.

Provision of Amniotic Fluid During Parenteral Nutrition Increases Weight Gain With Limited Effects on Gut Structure, Function, Immunity, and Microbiology in Newborn Preterm Pigs.

PubMed

Østergaard, Mette Viberg; Shen, Rene Liang; Støy, Ann Cathrine Findal; Skovgaard, Kerstin; Krych, Łukasz; Leth, Stine Sofie; Nielsen, Dennis Sandris; Hartmann, Bolette; Bering, Stine Brandt; Schmidt, Mette; Sangild, Per Torp

2016-05-01

Small enteral boluses with human milk may reduce the risk of subsequent feeding intolerance and necrotizing enterocolitis in preterm infants receiving parenteral nutrition (PN). We hypothesized that feeding amniotic fluid, the natural enteral diet of the mammalian fetus, will have similar effects and improve growth and gastrointestinal (GI) maturation in preterm neonates receiving PN, prior to the transition to milk feeding. Twenty-seven pigs, delivered by cesarean section at ~90% of gestation, were provided with PN and also fed boluses with amniotic fluid (AF; n = 13, 24-72 mL/kg/d) or no oral supplements (nil per os [NPO]; n = 14) until day 5 when blood, tissue, and fecal samples were collected for analyses. Body weight gain was 2.7-fold higher in AF vs NPO pigs. AF pigs showed slower gastric emptying, reduced meal-induced release of gastric inhibitory peptide and glucagon-like peptide 2, changed gut microbiota, and reduced intestinal permeability. There were no effects on GI weight, percentage mucosa, villus height, plasma citrulline, hexose absorptive capacity, and digestive enzymes. Intestinal interleukin (IL)-1β levels and expression of IL1B and IL8 were increased in AF pigs, while blood biochemistry and amino acid levels were minimally affected. Enteral boluses of AF were well tolerated in the first 5 days of life in preterm pigs receiving PN. Enteral provision of AF before the initiation of milk feeding may stimulate body growth and improve hydration in preterm infants receiving PN. Furthermore, it may improve GI motility and integrity, although most markers of GI maturation remain unchanged. © 2015 American Society for Parenteral and Enteral Nutrition.

Development of a programmable standard of ultra-low capacitance values.

PubMed

Khan, M S; Séron, O; Thuillier, G; Thévenot, O; Gournay, P; Piquemal, F

2017-05-01

A set of ultra-low value capacitance standards together with a programmable coaxial multiplexer (mux) have been developed. The mux allows the connection of these capacitances in parallel configuration and they together form the programmable capacitance standard. It is capable of producing decadic standard capacitances from 10 aF to at least 0.1 pF, which are later used to calibrate commercial precision capacitance bridges. This paper describes the realization and the characterization of this standard together with results obtained during the calibration of Andeen-Hagerling AH2700A bridges with a maximum uncertainty of 0.8 aF for all the capacitances generated ranging from 10 aF to 0.1 pF, at 1 kHz. These latter could be then integrated to functionalized AFMs or probe stations for quantitative capacitance measurements. Sources of uncertainties of the programmable capacitance standard, such as parasitic effects due to stray impedances, are evaluated and a method to overcome these hindrances is also discussed.

76 FR 36410 - Value Engineering

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

...-2011-0046] RIN 2125-AF40 Value Engineering AGENCY: Federal Highway Administration (FHWA), DOT. ACTION... regulations to enhance the integration of value engineering (VE) analysis in the planning and development of...-131 on Value Engineering. These revisions will also address certain findings contained in a 2007...

77 FR 15250 - Value Engineering

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

...-2011-0046] RIN 2125-AF40 Value Engineering AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Final rule. SUMMARY: This rule updates regulations to enhance the integration of value engineering (VE... Office of Management and Budget (OMB) Circular A-131 on Value Engineering. These revisions also will...

Intraoperative Inducibility of Atrial Fibrillation Does Not Predict Early Postoperative Atrial Fibrillation.

PubMed

Lanters, Eva A H; Teuwen, Christophe P; Yaksh, Ameeta; Kik, Charles; van der Does, Lisette J M E; Mouws, Elisabeth M J P; Knops, Paul; van Groningen, Nicole J; Hokken, Thijmen; Bogers, Ad J J C; de Groot, Natasja M S

2018-03-10

Early postoperative atrial fibrillation (EPoAF) is associated with thromboembolic events, prolonged hospitalization, and development of late PoAF (LPoAF). It is, however, unknown if EPoAF can be predicted by intraoperative AF inducibility. The aims of this study are therefore to explore (1) the value of intraoperative inducibility of AF for development of both EPoAF and LPoAF and (2) the predictive value of de novo EPoAF for recurrence of LPoAF. Patients (N=496, 75% male) undergoing cardiothoracic surgery for coronary and/or valvular heart disease were included. AF induction was attempted by atrial pacing, before extracorporeal circulation. All patients were on continuous rhythm monitoring until discharge to detect EPoAF. During a follow-up period of 2 years, LPoAF was detected by ECGs and Holter recordings. Sustained AF was inducible in 56% of patients. There was no difference in patients with or without AF before surgery ( P =0.159), or between different types of surgery ( P =0.687). In patients without a history of AF, incidence of EPoAF and LPoAF was 37% and 2%, respectively. EPoAF recurred in 58% patients with preoperative AF, 53% developed LPoAF. There were no correlations between intraoperative inducibility and EPoAF or LPoAF ( P >0.05). EPoAF was not correlated with LPoAF in patients without a history of AF ( P =0.116), in contrast to patients with AF before surgery ( P <0.001). Intraoperative AF inducibility does not predict development of either EPoAF or LPoAF. In patients with AF before surgery, EPoAF is correlated with LPoAF recurrences. This correlation is absent in patients without AF before surgery. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Using an Atrial Fibrillation Decision Support Tool for Thromboprophylaxis in Atrial Fibrillation: Effect of Sex and Age.

PubMed

Eckman, Mark H; Lip, Gregory Y H; Wise, Ruth E; Speer, Barbara; Sullivan, Megan; Walker, Nita; Kissela, Brett; Flaherty, Matthew L; Kleindorfer, Dawn; Baker, Peter; Ireton, Robert; Hoskins, Dave; Harnett, Brett M; Aguilar, Carlos; Leonard, Anthony; Arduser, Lora; Steen, Dylan; Costea, Alexandru; Kues, John

2016-05-01

To assess the appropriateness of oral anticoagulant therapy (OAT) in women and elderly adults, looking for patterns of undertreatment or unnecessary treatment. Retrospective cohort study. Primary care practices of an academic healthcare system. Adults (aged 28-93) with nonvalvular atrial fibrillation (AF) seen between March 2013 and February 2014 (N = 1,585). Treatment recommendations were made using an AF decision support tool (AFDST) based on projections of quality-adjusted life expectancy calculated using a decision analytical model that integrates individual-specific risk factors for stroke and hemorrhage. Treatment was discordant from AFDST-recommended treatment in 45% (326/725) of women and 39% (338/860) of men (P = .02). Although current treatment was discordant from recommended in 35% (89/258) of participants aged 85 and older and in 43% (575/1,328) of those younger than 85 (P = .01), many undertreated elderly adults were receiving aspirin as the sole antithrombotic agent. Physicians should understand that female sex is a significant risk factor for AF-related stroke and incorporate this into decision-making about thromboprophylaxis. Treating older adults with aspirin instead of OAT exposes them to significant risk of bleeding with little to no reduction in AF-related stroke risk. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

The non-equilibrium allele frequency spectrum in a Poisson random field framework.

PubMed

Kaj, Ingemar; Mugal, Carina F

2016-10-01

In population genetic studies, the allele frequency spectrum (AFS) efficiently summarizes genome-wide polymorphism data and shapes a variety of allele frequency-based summary statistics. While existing theory typically features equilibrium conditions, emerging methodology requires an analytical understanding of the build-up of the allele frequencies over time. In this work, we use the framework of Poisson random fields to derive new representations of the non-equilibrium AFS for the case of a Wright-Fisher population model with selection. In our approach, the AFS is a scaling-limit of the expectation of a Poisson stochastic integral and the representation of the non-equilibrium AFS arises in terms of a fixation time probability distribution. The known duality between the Wright-Fisher diffusion process and a birth and death process generalizing Kingman's coalescent yields an additional representation. The results carry over to the setting of a random sample drawn from the population and provide the non-equilibrium behavior of sample statistics. Our findings are consistent with and extend a previous approach where the non-equilibrium AFS solves a partial differential forward equation with a non-traditional boundary condition. Moreover, we provide a bridge to previous coalescent-based work, and hence tie several frameworks together. Since frequency-based summary statistics are widely used in population genetics, for example, to identify candidate loci of adaptive evolution, to infer the demographic history of a population, or to improve our understanding of the underlying mechanics of speciation events, the presented results are potentially useful for a broad range of topics. Copyright © 2016 Elsevier Inc. All rights reserved.

Pulmonary vein anatomy predicts freedom from atrial fibrillation using remote magnetic navigation for circumferential pulmonary vein ablation.

PubMed

Sohns, Christian; Sohns, Jan M; Bergau, Leonard; Sossalla, Samuel; Vollmann, Dirk; Lüthje, Lars; Staab, Wieland; Dorenkamp, Marc; Harrison, James L; O'Neill, Mark D; Lotz, Joachim; Zabel, Markus

2013-08-01

Multidetector computed tomography (MDCT) is frequently used to guide circumferential pulmonary vein ablation (PVA) for treatment of atrial fibrillation (AF) as it offers accurate visualization of the left atrial (LA) and pulmonary vein (PV) anatomy. This study aimed to identify if PV anatomy is associated with outcomes following PVA using remote magnetic navigation (RMN). We analysed data from 138 consecutive patients and 146 ablation procedures referred for PVA due to drug-refractory symptomatic AF (age 63 ± 11 years; 57% men; 69% paroxysmal AF). The RMN using the stereotaxis system and open-irrigated 3.5 mm ablation catheters was used in all procedures. Prior to PVA, all patients underwent electrocardiogram-gated 64-MDCT for assessment of LA dimensions, PV anatomy, and electro-anatomical image integration during the procedure. Regular PV anatomy was found in 68%, a common left PV ostium was detected in 26%, and variant anatomy of the right PVs was detected in 6%. After a mean follow-up of 337 ± 102 days, 63% of the patients maintained sinus rhythm after the initial ablation, and 83% when including repeat PVA. Although acutely successful PV isolation did not differ between anatomical subgroups (regular 3.5 ± 0.8 vs. variant 3.2 ± 1.3; P = 0.31), AF recurrence was significantly higher in patients with non-regular PV anatomy (P = 0.04, hazard ratio 1.72). Pulmonary vein anatomy did not influence complication rates. Pulmonary vein anatomy assessed by MDCT is a good predictor of AF recurrence after PVA using RMN.

Quantitative Autofluorescence Intensities in Acute Zonal Occult Outer Retinopathy vs Healthy Eyes

PubMed Central

Boudreault, Katherine; Schuerch, Kaspar; Zhao, Jin; Lee, Winston; Cabral, Thiago; Yannuzzi, Lawrence A.; Tsang, Stephen H.; Sparrow, Janet R.

2018-01-01

IMPORTANCE Acute zonal occult outer retinopathy (AZOOR) remains a challenging diagnosis. Early recognition of the disease depends on advances in imaging modalities that can improve phenotyping and contribute to the understanding of the underlying pathogenesis. OBJECTIVES To expand the range of approaches available to assist in the identification of AZOOR by multimodal imaging and to analyze the fundus lesions by quantifying short-wavelength fundus autofluorescence (quantitative fundus autofluorescence [qAF]) and spectral-domain optical coherence tomography. DESIGN, SETTING, AND PARTICIPANTS In this observational study, patients underwent imaging at Columbia University Medical Center between November 2010 and March 2016 and were analyzed between September 2015 and August 2016. Six patients diagnosed as having AZOOR were studied by qAF and spectral-domain optical coherence tomography and were compared with 30 age and race/ethnicity–matched controls from a database of 277 healthy control eyes. MAIN OUTCOMES AND MEASURES In unaffected regions of the macula, qAF was calculated within predetermined circularly arranged segments (qAF8). In addition, qAF was measured within specified regions of interest positioned at the autofluorescent lesion border (AZOOR line). Electroretinograms and electro-oculograms were recorded in 5 of 6 patients. RESULTS Among 6 patients (age range, 26–61 years; 4 female; 4 of white race/ethnicity, 1 Asian, and 1 Hispanic), 5 exhibited an autofluorescent AZOOR line in short-wavelength fundus autofluorescence images, delineating the peripapillary lesion. The mean (SD) region-of-interest qAF measured on the AZOOR line was 60 (26) times higher than in healthy control eyes (P = .03) at equivalent fundus locations. The qAF8 within nondiseased macular regions were within the normal range. At the lesion border, spectral-domain optical coherence tomography revealed a loss of outer retinal integrity in all patients. Single-flash cone b-wave latency and 30-Hz flicker latency responses were significantly delayed bilaterally. Lesions with smooth, homogeneous borders exhibited only minimal expansion in size over time, while the lesion in a patient with a heterogeneous border progressed more rapidly. CONCLUSIONS AND RELEVANCE The finding that qAF is elevated at the border between diseased and nondiseased retina in patients with AZOOR contributes to the understanding of the natural history of the disease. PMID:29075777

Human Cardiomyocytes Prior to Birth by Integration-Free Reprogramming of Amniotic Fluid Cells

PubMed Central

Jiang, Guihua; Herron, Todd J.; Di Bernardo, Julie; Walker, Kendal A.; O’Shea, K. Sue

2016-01-01

The establishment of an abundant source of autologous cardiac progenitor cells would represent a major advance toward eventual clinical translation of regenerative medicine strategies in children with prenatally diagnosed congenital heart disease. In support of this concept, we sought to examine whether functional, transgene-free human cardiomyocytes (CMs) with potential for patient-specific and autologous applications could be reliably generated following routine amniocentesis. Under institutional review board approval, amniotic fluid specimens (8–10 ml) at 20 weeks gestation were expanded and reprogrammed toward pluripotency using nonintegrating Sendai virus (SeV) expressing OCT4, SOX2, cMYC, and KLF4. Following exposure of these induced pluripotent stem cells to cardiogenic differentiation conditions, spontaneously beating amniotic fluid-derived cardiomyocytes (AF-CMs) were successfully generated with high efficiency. After 6 weeks, quantitative gene expression revealed a mixed population of differentiated atrial, ventricular, and nodal AF-CMs, as demonstrated by upregulation of multiple cardiac markers, including MYH6, MYL7, TNNT2, TTN, and HCN4, which were comparable to levels expressed by neonatal dermal fibroblast-derived CM controls. AF-CMs had a normal karyotype and demonstrated loss of NANOG, OCT4, and the SeV transgene. Functional characterization of SIRPA+ AF-CMs showed a higher spontaneous beat frequency in comparison with dermal fibroblast controls but revealed normal calcium transients and appropriate chronotropic responses after β-adrenergic agonist stimulation. Taken together, these data suggest that somatic cells present within human amniotic fluid can be used to generate a highly scalable source of functional, transgene-free, autologous CMs before a child is born. This approach may be ideally suited for patients with prenatally diagnosed cardiac anomalies. Significance This study presents transgene-free human amniotic fluid-derived cardiomyocytes (AF-CMs) for potential therapy in tissue engineering and regenerative medicine applications. Using 8–10 ml of amniotic fluid harvested at 20 weeks gestation from normal pregnancies, a mixed population of atrial, ventricular, and nodal AF-CMs were reliably generated after Sendai virus reprogramming toward pluripotency. Functional characterization of purified populations of beating AF-CMs revealed normal calcium transients and appropriate chronotropic responses after β-adrenergic agonist stimulation in comparison with dermal fibroblast controls. Because AF-CMs can be generated in fewer than 16 weeks, this approach may be ideally suited for eventual clinical translation at birth in children with prenatally diagnosed cardiac anomalies. PMID:27465073

FIELD MEASUREMENTS OF CONTAMINANT FLUX BY INTEGRAL PUMPING TESTS (SAN FRANCISCO, CA)

EPA Science Inventory

Current remedial techniques are unable to completely eliminate all dense nonaqueous phase liquid (DNAPL) from source zone areas and conflicting views on the benefits of partial DNAPL source zone remediation exist in the literature. A comparison of flux measurements before and af...

Contact force sensing for ablation of persistent atrial fibrillation: A randomized, multicenter trial.

PubMed

Conti, Sergio; Weerasooriya, Rukshen; Novak, Paul; Champagne, Jean; Lim, Hong Euy; Macle, Laurent; Khaykin, Yaariv; Pantano, Alfredo; Verma, Atul

2018-02-01

Impact of contact force sensing (CFS) on ablation of persistent atrial fibrillation (PeAF) is unknown. The purpose of the TOUCH AF (Therapeutic Outcomes Using Contact force Handling during Ablation of Persistent Atrial Fibrillation) randomized trial was to compare CFS-guided ablation to a CFS-blinded strategy. Patients (n = 128) undergoing first-time ablation for persistent AF were randomized to a CFS-guided vs CFS-blinded strategy. In the CFS-guided procedure, operators visualized real-time force data. In the blinded procedure, force data were hidden. Wide antral pulmonary vein isolation plus a roof line were performed. Patients were followed at 3, 6, 9, and 12 months with clinical visit, ECG, and 48-hour Holter monitoring. The primary endpoint was cumulative radiofrequency (RF) time for all procedures. Atrial arrhythmia >30 seconds after 3 months was a recurrence. PeAF was continuous for 26 weeks (interquartile range [IQR] 13-52), and left atrial size was 45 ± 5 mm. Force in the CFS-blinded and CFS-guided arms was 12 g [IQR 6-20] and 14 g [IQR 9-20] (P = .10), respectively. Total RF time did not differ between CFS-guided and CFS-blinded groups (49 ± 14 min vs 50 ± 20 min, respectively; P = .70). Single procedure freedom from atrial arrhythmia was 60% in the CFS-guided arm and 63% in the CFS-blinded arm off drugs. Lesions with gaps were associated with significantly less force (11.4 g [IQR 6-19] vs 13.2 g [IQR 8-20], respectively; P = .0007) and less force-time integral (174 gs [IQR 91-330] vs 210 gs [IQR 113-388], respectively; P <.001). CFS-guided ablation resulted in no difference to RF time or 12-month outcome. Lower force/force-time integral was associated with significantly more gaps. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Development of a biochip-based assay integrated in a global strategy for identification of fusion transcripts in acute myeloid leukemia: a work flow for acute myeloid leukemia diagnosis.

PubMed

Giusiano, S; Formisano-Tréziny, C; Benziane, A; Maroc, N; Picard, C; Hermitte, F; Taranger-Charpin, C; Gabert, J

2010-08-01

Three major types of rearrangements are involved in acute myeloid leukemias (AML): t(8;21)(q22;q22), inv(16)(p13q22), and 11q23/MLL abnormalities. Their precise identification becomes essential for diagnosis, prognosis, and therapeutic choices. Resulting fusion transcripts (FT) are also powerful markers for monitoring the efficacy of treatment, the minimal residual disease (MRD) and could become therapeutic targets. Today, the challenge is to propose an individual follow-up for each patient even for those with a rare fusion event. In this study, we propose a biochip-based assay integrated in a global strategy for identification of rare FT in AML, after fluorescence in situ hybridization detection, as described by the World Health Organization classification. Using cell lines, we developed and validated a biochip-based assay called the AMLFusionChip that identifies every FT of AML1-ETO, CBFbeta-MYH11 as well as MLL-AF9, MLL-ENL, MLL-AF6, and MLL-AF10. The original design of our AMLFusionChip.v01 enables the identification of these FT wherever the breakpoint on the partner gene may be. In case of biochip negative result, our 3'RACE amplification strategy enables to clone and then sequence the new translocation partner. This AMLFusionChip strategy fits into the concept of personalized medicine for the largest number of patients.

75 FR 71090 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-22

... Office, Office of Warfighting Integration and Chief Information officer, ATTN: SAF/XCPPI, 1800 Air Force..., Alternate OSD Federal Register Liaison Officer, Department of Defense. F065 AF FMP System name: Financial..., SD 57706-4853. Air Force Financial Services Center Information Technology Team and the 28th...

75 FR 60437 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... Office, Office of Warfighting Integration and Chief Information officer, ATTN: SAF/XCPPI, 1800 Air Force... Federal Register Liaison Officer, Department of Defense. F065 AF FMP B System name: Customer Relationship...D Pay and Allowances Policy and Procedures; DoD Financial Management Regulation (DoDFMR) 7000.14-R...

Integrated database for identifying candate genes for Aspergillus flavus resistance in maize

USDA-ARS?s Scientific Manuscript database

Aspergillus flavus Link:Fr, an opportunistic fungus that produces aflatoxin, is pathogenic to maize and other oilseed crops. Aflatoxin is a potent carcinogen, and its presence markedly reduces the value of grain. Understanding and enhancing host resistance to A. flavus infection and/or subsequent af...

Radiofrequency catheter ablation of atrial fibrillation: Electrical modification suggesting transmurality is faster achieved with remote magnetic catheter in comparison with contact force use.

PubMed

Bun, Sok-Sithikun; Ayari, Anis; Latcu, Decebal Gabriel; Errahmouni, Abdelkarim; Saoudi, Nadir

2017-07-01

Remote magnetic navigation (RMN) and contact force (CF) sensing catheters are available technologies for radiofrequency (RF) catheter ablation of atrial fibrillation (AF). Our purpose was to compare time to electrogram (EGM) modification suggesting transmural lesions between RMN and CF-guided AF ablation. A total of 1,008 RF applications were analyzed in 21 patients undergoing RMN (n = 11) or CF-guided ablation (n = 10) for paroxysmal AF. All procedures were performed in sinus rhythm during general anesthesia. Time to EGM modification was measured until transmurality criteria were fulfilled: (1) complete disappearance of R if initial QR morphology; (2) diminution > 75% of R if initial QRS morphology; (3) complete disappearance of R' of initial RSR' morphology. Impedance drop as well as force time integral (FTI) were also assessed for each application. Mean CF at the beginning of each RF application in the CF group was 11 ± 2 g and mean FTI per application was 488 ± 163 gs. Time to EGM modification was significantly shorter in the RMN group (4.52 ± 0.1 seconds vs. 5.6 ± 0.09 seconds; P < 0.00001). There was no significant difference between other procedural parameters. Remote magnetic AF ablation is associated with faster EGM modification suggesting transmurality than optimized CF and FTI-guided catheter ablation. © 2017 Wiley Periodicals, Inc.

European Society of Cardiology smartphone and tablet applications for patients with atrial fibrillation and their health care providers

PubMed Central

Kotecha, Dipak; Chua, Winnie W L; Fabritz, Larissa; Hendriks, Jeroen; Casadei, Barbara; Schotten, Ulrich; Vardas, Panos; Heidbuchel, Hein; Dean, Veronica; Kirchhof, Paulus

2018-01-01

Abstract We are in the midst of a digital revolution in health care, although the application of new and useful technology in routine clinical practice is variable. The Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly (CATCH ME) Consortium, in collaboration with the European Society of Cardiology (ESC), has funded the creation of two applications (apps) in atrial fibrillation (AF) for use in smartphones and tablets. The patient app aims to enhance patient education, improve communication between patients and health care professionals, and encourage active patient involvement in the management of their condition. The health care professional app is designed as an interactive management tool incorporating the new ESC Practice Guidelines on AF and supported by the European Heart Rhythm Association (EHRA), with the aim of improving best practice approaches for the care of patients with AF. Both stand-alone apps are now freely available for Android and iOS devices though the Google Play, Amazon, and Apple stores. In this article, we outline the rationale for the design and implementation of these apps. Our objective is to demonstrate the value of integrating novel digital technology into clinical practice, with the potential for patient engagement, optimization of pharmacological and interventional therapy in AF, and ultimately to improve patient outcomes. PMID:29040548

The Acquisition Cost-Estimating Workforce. Census and Characteristics

DTIC Science & Technology

2009-01-01

Abbreviations AAC Air Armament Center ACAT acquisition category ACEIT Automated Cost Estimating Integrated Tools AF Air Force AFB Air Force Base AFCAA Air...3 3 4 Automated Cost Estimating Integrated Tools ( ACEIT ) 0 1 12 6 Tecolotea training 0 0 10 5 Other 3 13 24 18 No training 18 4 29 18 Total 100 100...other sources, including AFIT, ACEIT ,9 or the contracting agency that employed them. The remain- ing 29 percent reported having received no training

DOD Business Systems Modernization: Additional Action Needed to Achieve Intended Outcomes

DTIC Science & Technology

2015-07-01

including greater operational efficiencies and cost savings. View GAO-15-627. For more information, contact Carol R. Cha at (202) 512-4456 or chac @gao.gov...report, please contact me at (202) 512-4456 or chac @gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found...Personnel and Pay System - Army (IPPS-A), Integrated Personnel and Pay System - Navy (IPPS- N ), Air Force Integrated Personnel and Pay System (AF-IPPS

Non-Deterministic, Non-Traditional Methods (NDNTM)

NASA Technical Reports Server (NTRS)

Cruse, Thomas A.; Chamis, Christos C. (Technical Monitor)

2001-01-01

The review effort identified research opportunities related to the use of nondeterministic, nontraditional methods to support aerospace design. The scope of the study was restricted to structural design rather than other areas such as control system design. Thus, the observations and conclusions are limited by that scope. The review identified a number of key results. The results include the potential for NASA/AF collaboration in the area of a design environment for advanced space access vehicles. The following key points set the context and delineate the key results. The Principal Investigator's (PI's) context for this study derived from participation as a Panel Member in the Air Force Scientific Advisory Board (AF/SAB) Summer Study Panel on 'Whither Hypersonics?' A key message from the Summer Study effort was a perceived need for a national program for a space access vehicle whose operating characteristics of cost, availability, deployability, and reliability most closely match the NASA 3rd Generation Reusable Launch Vehicle (RLV). The Panel urged the AF to make a significant joint commitment to such a program just as soon as the AF defined specific requirements for space access consistent with the AF Aerospace Vision 2020. The review brought home a concurrent need for a national vehicle design environment. Engineering design system technology is at a time point from which a revolution as significant as that brought about by the finite element method is possible, this one focusing on information integration on a scale that far surpasses current design environments. The study therefore fully supported the concept, if not some of the details of the Intelligent Synthesis Environment (ISE). It became abundantly clear during this study that the government (AF, NASA) and industry are not moving in the same direction in this regard, in fact each is moving in its own direction. NASA/ISE is not yet in an effective leadership position in this regard. However, NASA does have complementary software interoperability efforts that should be a part of any major ISE program. Software standards that assure interoperability of data systems and modeling representations are enabling for the proposed research advocated herein and should be a major element in the ISE initiative. The international standard for data interchange is known by the acronym 'STEP.' The NASA participation and lead for that effort is at the Goddard Space Flight Center. NASA/GRC is leading an effort to define CAD geometry standards through the Object Management Group (OMG). To enable the design environment so necessary to the above national vision for a unique space vehicle will require an integrating software environment with interoperability standards that allow the development and widespread deployment of tools and toolsets, rather than traditional "shrink-wrapped" software used by engineers today.

Mutations in GPR143/OA1 and ABCA4 Inform Interpretations of Short-Wavelength and Near-Infrared Fundus Autofluorescence

PubMed Central

Paavo, Maarjaliis; Zhao, Jin; Kim, Hye Jin; Lee, Winston; Zernant, Jana; Cai, Carolyn; Allikmets, Rando; Tsang, Stephen H.; Sparrow, Janet R.

2018-01-01

Purpose We sought to advance interpretations and quantification of short-wavelength fundus autofluorescence (SW-AF) emitted from bisretinoid lipofuscin and near-infrared autofluoresence (NIR-AF) originating from melanin. Methods Carriers of mutations in X-linked GPR143/OA1, a common form of ocular albinism; patients with confirmed mutations in ABCA4 conferring increased SW-AF; and subjects with healthy eyes were studied. SW-AF (488 nm excitation, 500–680 nm emission) and NIR-AF (excitation 787 nm, emission >830 nm) images were acquired with a confocal scanning laser ophthalmoscope. SW-AF images were analyzed for quantitative autofluoresence (qAF). Analogous methods of image acquisition and analysis were performed in albino and pigmented Abca4−/− mice and wild-type mice. Results Quantitation of SW-AF (qAF), construction of qAF color-coded maps, and examination of NIR-AF images from GPR143/OA1 carriers revealed mosaics in which patches of fundus exhibiting NIR-AF signal had qAF levels within normal limits whereas the hypopigmented areas in the NIR-AF image corresponded to foci of elevated qAF. qAF also was increased in albino versus pigmented mice. Although melanin contributes to fundus infrared reflectance, the latter appeared to be uniform in en face reflectance images of GPR143/OA1-carriers. In patients diagnosed with ABCA4-associated disease, NIR-AF increased in tandem with increased qAF originating in bisretinoid lipofuscin. Similarly in Abca4−/− mice having increased SW-AF, NIR-AF was more pronounced than in wild-type mice. Conclusions These studies corroborate RPE melanin as the major source of NIR-AF but also indicate that bisretinoid lipofuscin, when present at sufficient concentrations, contributes to the NIR-AF signal. Ocular melanin attenuates the SW-AF signal.

Screening for asymptomatic atrial fibrillation while monitoring the blood pressure at home: trial of regular versus irregular pulse for prevention of stroke (TRIPPS 2.0).

PubMed

Wiesel, Joseph; Abraham, Saji; Messineo, Frank C

2013-06-01

Asymptomatic atrial fibrillation (AF) is a common cause of strokes. Physician screening for AF has been recommended. Home screening for AF may increase the likelihood of detecting asymptomatic AF in patients at risk for stroke because of AF. The aim of this study was to assess the feasibility and accuracy of screening for AF when taking home blood pressure (BP) measurements using an automatic AF-detecting BP monitor. Subjects aged >64 years or those with hypertension, diabetes, congestive heart failure, or previous stroke were enrolled by their primary physicians and given the AF-BP monitor and an electrocardiographic event monitor to use at home for 30 days. The AF-BP monitor reading was compared with the electrocardiographic reading to calculate the sensitivity and specificity of the device for detecting AF. A total of 160 subjects were enrolled, with 10 withdrawing, 1 excluded, and 10 with no AF-BP monitor logs or electrocardiographic recordings. Of the 139 subjects included, 14 had known AF. There was a total of 3,316 days with AF-BP monitor readings and electrocardiographic readings. On the basis of the initial daily AF-BP monitor readings, the AF-BP monitor demonstrated sensitivity of 99.2% and specificity of 92.9% for detecting AF. Two subjects with no histories of AF had AF-BP monitor readings of AF that were confirmed by the electrocardiographic monitor. One of these subjects was started on warfarin. In conclusion, home screening for asymptomatic AF while taking BP measurements can be performed accurately. This can be used to detect new AF, allowing treatment with anticoagulation to reduce the future risk for stroke. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Computer Assisted Exercise Environment for Terrorist Attack Consequence Management

DTIC Science & Technology

2006-09-01

security and crisis management. Fig. 3. Third Generation SSR for Integrated Security Sector MoD MoI MoEM MoFA Special Services Integrated Security...Ministries: MoEM , MoI, MoD, MH, MoEW, MoE, MoAF National Media, NGOs, other agencies District EOC / LEMA MHS/IDS/WIS Field EOC MHS/IDS/WIS MHS IDS...SRA EDA DG Environment ... EU SR Fund MoD MoI MoE&S MoEM ... National USA Great Britain Netherlands Germany ... Bilateral BSEC Stab. Pact ... Regional

Magnetic viscosity phenomena in exchange coupled CoFe /MnIr bilayers

NASA Astrophysics Data System (ADS)

Kim, Dong Young; Kim, C. O.; Tsunoda, M.; Yamaguchi, M.; Yabugami, S.; Takahashi, M.

2007-05-01

The complex permeability spectra were measured in the low (10Hz-1MHz) and microwave (100MHz-9GHz) frequency ranges in CoFe /MnIr bilayers. The low frequency permeability spectra showed the magnetic viscosity effect below the critical antiferromagnet thickness (tcAF), but not at tAFtcAF. The discrepancies between dynamic and quasistatic measurements of the Jc only begin to appear in the vicinity of the tcAF and dominate at tAF

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

PubMed

Steinberg, Benjamin A; Gao, Haiyan; Shrader, Peter; Pieper, Karen; Thomas, Laine; Camm, A John; Ezekowitz, Michael D; Fonarow, Gregg C; Gersh, Bernard J; Goldhaber, Samuel; Haas, Sylvia; Hacke, Werner; Kowey, Peter R; Ansell, Jack; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Turpie, Alexander; Verheugt, Freek; Piccini, Jonathan P; Kakkar, Ajay; Peterson, Eric D; Fox, Keith A A

2017-12-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA 2 DS 2 -VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA 2 DS 2 -VASc=0 and 69% and 87% for CHA 2 DS 2 -VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Correlations Among Near-Infrared and Short-Wavelength Autofluorescence and Spectral-Domain Optical Coherence Tomography in Recessive Stargardt Disease

PubMed Central

Duncker, Tobias; Marsiglia, Marcela; Lee, Winston; Zernant, Jana; Tsang, Stephen H.; Allikmets, Rando; Greenstein, Vivienne C.; Sparrow, Janet R.

2014-01-01

Purpose. Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in retinal pigment epithelium (RPE) and near-infrared (NIR) AF from melanin. In patients with recessive Stargardt disease (STGD1), we correlated SW-AF and NIR-AF with structural information obtained by spectral-domain optical coherence tomography (SD-OCT). Methods. Twenty-four STGD1 patients (45 eyes; age 8 to 61 years) carrying confirmed disease-associated ABCA4 mutations were studied prospectively. Short-wavelength AF, NIR-AF, and SD-OCT images were acquired. Results. Five phenotypes were identified according to features of the central lesion and extent of fundus change. Central zones of reduced NIR-AF were typically larger than areas of diminished SW-AF and reduced NIR-AF usually approximated areas of ellipsoid zone (EZ) loss identified by SD-OCT (group 1; r, 0.93, P < 0.0001). In patients having a central lesion with overlapping parafoveal rings of increased NIR-AF and SW-AF (group 3), the extent of EZ loss was strongly correlated with the inner diameter of the NIR-AF ring (r, 0.89, P < 0.0001) and the eccentricity of the outer border of the NIR-AF ring was greater than that of the SW-AF ring. Conclusions. Lesion areas were more completely delineated in NIR-AF images than with SW-AF. In most cases, EZ loss was observed only at locations where NIR-AF was reduced or absent, indicating that RPE cell atrophy occurs in advance of photoreceptor cell degeneration. Because SW-AF was often increased within the central area of EZ disruption, degenerating photoreceptor cells may produce lipofuscin at accelerated levels. Consideration is given to mechanisms underlying hyper–NIR-AF in conjunction with increased SW-AF. PMID:25342616

Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association.

PubMed

Chen, Lin Y; Chung, Mina K; Allen, Larry A; Ezekowitz, Michael; Furie, Karen L; McCabe, Pamela; Noseworthy, Peter A; Perez, Marco V; Turakhia, Mintu P

2018-05-15

Our understanding of the risk factors and complications of atrial fibrillation (AF) is based mostly on studies that have evaluated AF in a binary fashion (present or absent) and have not investigated AF burden. This scientific statement discusses the published literature and knowledge gaps related to methods of defining and measuring AF burden, the relationship of AF burden to cardiovascular and neurological outcomes, and the effect of lifestyle and risk factor modification on AF burden. Many studies examine outcomes by AF burden classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively, AF burden can be defined by longest duration, number of AF episodes during a monitoring period, and the proportion of time an individual is in AF during a monitoring period (expressed as a percentage). Current guidelines make identical recommendations for anticoagulation regardless of AF pattern or burden; however, a review of recent evidence suggests that higher AF burden is associated with higher risk of stroke. It is unclear whether the risk increases continuously or whether a threshold exists; if a threshold exists, it has not been defined. Higher burden of AF is also associated with higher prevalence and incidence of heart failure and higher risk of mortality, but not necessarily lower quality of life. A structured and comprehensive risk factor management program targeting risk factors, weight loss, and maintenance of a healthy weight appears to be effective in reducing AF burden. Despite this growing understanding of AF burden, research is needed into validation of definitions and measures of AF burden, determination of the threshold of AF burden that results in an increased risk of stroke that warrants anticoagulation, and discovery of the mechanisms underlying the weak temporal correlations of AF and stroke. Moreover, developments in monitoring technologies will likely change the landscape of long-term AF monitoring and could allow better definition of the significance of changes in AF burden over time. © 2018 American Heart Association, Inc.

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

Electro-Spark Deposited Coatings for Replacement of Chrome Electroplating

DTIC Science & Technology

2005-06-01

2.6 0.4 2.2 Thickness uniformity (A-F) 2.8/0.8 2.8/0.8 6.3/0 6.5/0.4 2 to 0 3.9/0.4 Coating integrity (A-F) A A- F C - D A- Defects/mm F D + F D + F B...or width of the wear scar (cm), h is the height or depth of the wear scar (cm), and c is the circumference of the wear scar (cm) where c = "rrd, and d ...inerS4C *2 Panelb MHC583010 -,,IN 3 4853 0.42 roiness 1)N32-15m x c -e sca. 3) &wN x Deb 1nQ withn sar Dein HxW 1).057n*~ 3)211200 12 ve 2 Panl 2 EJC .5 D

Foraging behavior of lactating South American sea lions (Otaria flavescens) and spatial-temporal resource overlap with the Uruguayan fisheries

NASA Astrophysics Data System (ADS)

Riet-Sapriza, Federico G.; Costa, Daniel P.; Franco-Trecu, Valentina; Marín, Yamandú; Chocca, Julio; González, Bernardo; Beathyate, Gastón; Louise Chilvers, B.; Hückstadt, Luis A.

2013-04-01

Resource competition between fisheries and marine mammal continue to raise concern worldwide. Understanding this complex conflict requires data on spatial and dietary overlap of marine mammal and fisheries. In Uruguay the South American sea lions population has been dramatically declining over the past decade. The reasons for this population decline are unknown but may include the following: (1) direct harvesting; (2) reduced prey availability and distribution as a consequence of environmental change; or (3) biological interaction with fisheries. This study aims to determine resource overlap and competition between South American sea lions (SASL, Otaria flavescens, n=10) and the artisanal fisheries (AF), and the coastal bottom trawl fisheries (CBTF). We integrated data on sea lions diet (scat analysis), spatial and annual consumption estimates; and foraging behavior-satellite-tracking data from lactating SASL with data on fishing effort areas and fisheries landings. We found that lactating SASL are benthic divers and forage in shallow water within the continental shelf. SASL's foraging areas overlapped with CBTF and AF fisheries operational areas. Dietary analysis indicated a high degree of overlap between the diet of SASL and the AF and CBTF fisheries catch. The results of our work show differing degrees of spatial resource overlap with AF and CBTF, highlighting that there are differences in potential impact from each fishery; and that different management/conservation approaches may need to be taken to solve the fisheries-SASL conflict.

European Society of Cardiology smartphone and tablet applications for patients with atrial fibrillation and their health care providers.

PubMed

Kotecha, Dipak; Chua, Winnie W L; Fabritz, Larissa; Hendriks, Jeroen; Casadei, Barbara; Schotten, Ulrich; Vardas, Panos; Heidbuchel, Hein; Dean, Veronica; Kirchhof, Paulus

2018-02-01

We are in the midst of a digital revolution in health care, although the application of new and useful technology in routine clinical practice is variable. The Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly (CATCH ME) Consortium, in collaboration with the European Society of Cardiology (ESC), has funded the creation of two applications (apps) in atrial fibrillation (AF) for use in smartphones and tablets. The patient app aims to enhance patient education, improve communication between patients and health care professionals, and encourage active patient involvement in the management of their condition. The health care professional app is designed as an interactive management tool incorporating the new ESC Practice Guidelines on AF and supported by the European Heart Rhythm Association (EHRA), with the aim of improving best practice approaches for the care of patients with AF. Both stand-alone apps are now freely available for Android and iOS devices though the Google Play, Amazon, and Apple stores. In this article, we outline the rationale for the design and implementation of these apps. Our objective is to demonstrate the value of integrating novel digital technology into clinical practice, with the potential for patient engagement, optimization of pharmacological and interventional therapy in AF, and ultimately to improve patient outcomes. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

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

Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

PubMed

Hansen, Brian J; Zhao, Jichao; Csepe, Thomas A; Moore, Brandon T; Li, Ning; Jayne, Laura A; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A; Simonetti, Orlando P; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L; Weiss, Raul; Hummel, John D; Fedorov, Vadim V

2015-09-14

The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts

PubMed Central

Hansen, Brian J.; Zhao, Jichao; Csepe, Thomas A.; Moore, Brandon T.; Li, Ning; Jayne, Laura A.; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A.; Simonetti, Orlando P.; Higgins, Robert S.D.; Kilic, Ahmet; Mohler, Peter J.; Janssen, Paul M.L.; Weiss, Raul; Hummel, John D.; Fedorov, Vadim V.

2015-01-01

Aims The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial–epicardial (Endo–Epi) mapping coupled with high-resolution 3D structural imaging. Methods and results Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43–72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo–Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7–6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30–100 µM) perfusion. Dual-sided sub-Endo–sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or ‘breakthrough’ patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Conclusions Integrated 3D structural–functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. PMID:26059724

High burden of Aspergillus fumigatus infection among chronic respiratory diseases.

PubMed

Fukuda, Yosuke; Homma, Tetsuya; Suzuki, Shintaro; Takuma, Takahiro; Tanaka, Akihiko; Yokoe, Takuya; Ohnishi, Tsukasa; Niki, Yoshihito; Sagara, Hironori

2018-01-01

Aspergillus fumigatus (AF) is a ubiquitous fungus in our environment and causes severe airway disorders. Chronic respiratory diseases (CRDs) are a series of chronic airway and lung diseases. Although both are chronic disorders, however, the relationships between AF and CRDs are still unclear. Therefore, we examined 104 Aspergillus species (spp.) isolated samples in our hospital during three consecutive years to further elucidate the relationships between Aspergillus spp. and CRDs. Based on sample isolates, we then grouped these into two groups, AF and non-AF, to retrospectively analyse the clinical features and to clarify the relationships between AF and CRDs. Importantly, the manifestation of CRD was more frequent in the AF group than in the non-AF group ( p = 0.035). Among CRDs, lung fibrosis was more evident in the AF group ( p = 0.025). Moreover, diabetes mellitus was tended to be evident in AF group than non-AF group ( p = 0.035). In conclusion, CRDs, especially lung fibrosis, were highly prevalent in AF group than non-AF group.

Integrated instrument for dynamic light scattering and natural fluorescence measurements

NASA Astrophysics Data System (ADS)

Rovati, Luigi; Pollonini, Luca; Ansari, Rafat R.

2001-06-01

Over the past two decades, great efforts have been made in ophthalmology to use optical techniques based on dynamic light scattering and tissue natural fluorescence for early (at molecular level) diagnosis of ocular pathologies. In our previous studies, the relationship between the corneal AF and DLS decay widths of ocular tissues were established by performing measurements on diabetes mellitus patients. In those studies, corneal AF mean intensities were significantly correlated with DLS decay width measurements for each diabetic retinopathy grade in the vitreous and in the cornea. This suggested that the quality of the diagnosis could be significantly improved by properly combining these two powerful techniques into a single instrument. Our approach is based on modifying a commercial scanning ocular fluorometer (Fluorotron Master, Ocumetrics Inc., CA, USA) to include both techniques in the same scanning unit. This configuration provides both DLS and AF real time measurements from the same ocular volume: they can be located in each section of the optical axis of the eye from the cornea to the retina. In this paper, the optical setup of the new system is described and preliminary in-vitro and in-vivo measurements are presented.

An Implicit Characteristic Based Method for Electromagnetics

NASA Technical Reports Server (NTRS)

Beggs, John H.; Briley, W. Roger

2001-01-01

An implicit characteristic-based approach for numerical solution of Maxwell's time-dependent curl equations in flux conservative form is introduced. This method combines a characteristic based finite difference spatial approximation with an implicit lower-upper approximate factorization (LU/AF) time integration scheme. This approach is advantageous for three-dimensional applications because the characteristic differencing enables a two-factor approximate factorization that retains its unconditional stability in three space dimensions, and it does not require solution of tridiagonal systems. Results are given both for a Fourier analysis of stability, damping and dispersion properties, and for one-dimensional model problems involving propagation and scattering for free space and dielectric materials using both uniform and nonuniform grids. The explicit Finite Difference Time Domain Method (FDTD) algorithm is used as a convenient reference algorithm for comparison. The one-dimensional results indicate that for low frequency problems on a highly resolved uniform or nonuniform grid, this LU/AF algorithm can produce accurate solutions at Courant numbers significantly greater than one, with a corresponding improvement in efficiency for simulating a given period of time. This approach appears promising for development of dispersion optimized LU/AF schemes for three dimensional applications.

Resonance energy transfer between the active sites of creatine kinase from rabbit brain.

PubMed

Grossman, S H

1990-09-03

Resonance energy transfer was measured between the active site domains of the brain isozyme of creatine kinase (CK-BB). The reactive thiol near the active sites, one on each subunit of the dimeric protein, was derivatized using 5-[2-[iodoacetyl)amino)ethyl]aminonaphthalene-1-sulfonic acid (AED), 2-[4'-iodoacetamidoanilino]naphthalene-6-sulfonic acid (AANS) and 5-iodoacetamidofluorescein (AF). Suitable donor/acceptor protein conjugated hybrids were prepared by controlled kinetics producing CK-BB-AED/AF and CK-BB-AANS/AF. Transfer efficiencies, measured from the quenching of the donor lifetime and steady-state sensitized acceptor emission, ranged from 0.10 to 0.17. From determination of the donor/acceptor overlap integrals, donor quantum yields and attempts to delimit the orientation factor using steady-state and phase-resolved anisotropy measurements, it was found that a suitable estimate of the range between the active sites was between 45 and 57 A. This range is similar to that reported previously for the muscle isozyme of creatine kinase (Grossman, S.H. (1989) Biochemistry 28, 4894-4902) but is a significantly greater distance than detected for the hybrid, myocardial specific isozyme (Grossman, S.H. (1983) Biochemistry 22, 5369-5375).

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.

Aspergillus fumigatus (Af) Hydroxamate Siderophores Protect Formation of Af Biofilms from the Pseudomonas aeruginosa (Pa) Product Pyoverdine

PubMed Central

Sass, Gabriele; Stevens, David A

2017-01-01

Abstract Background Pa and Af are pathogens frequently found together in airways of immunocompromised patients and patients with cystic fibrosis (CF). Hence, interactions of Pa and Af require understanding. Both Pa and Af are crucially dependent on the availability of iron, and therefore are competitors in their microenvironment. We have shown, using deletion mutants of Pa, that the Pa siderophore pyoverdine, the dominant Pa inhibitor of Af, interferes with Af biofilms by iron chelation, and denial of iron to the fungus. Methods Protective compounds in Af supernatants were evaluated using assays for the quantification of Af biofilm metabolism by XTT measurement, spectrometric pyoverdine measurement, as well as Chrome Azorole S (CAS) assay for the determination of siderophore production. Results Here we provide evidence that whereas iron usage by Af promotes pyoverdine production by Pa, Af has developed a defense mechanism against anti-fungal pyoverdine effects. The ability of Af to produce hydroxamate siderophores, and shed these into the surrounding medium, where they sequester and transport iron, is a key factor for Af self-defense against Pa. Under low iron conditions, such as in the presence of high amounts of the Pa siderophore pyoverdine, siderophore-bound iron is then fed to Af, protecting the fungus from iron starvation. Af with a deletion mutation in sidA, a gene essential for the production of hydroxamate siderophores, was significantly more sensitive to Pa supernatants, as well as pure pyoverdine, than wild-type Af. Af supernatants, produced in the presence of celastrol, an inhibitor of SidA-generated biosynthesis of siderophores, or produced by the sidA mutant, were not able to protect Af from iron starvation. Conclusion Interference with the iron-dependent Af self-defense mechanism might represent a new approach for therapy against aspergillosis. Disclosures All authors: No reported disclosures.

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.

Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Soliman, Elsayed Z; Prineas, Ronald J; Case, L Douglas; Zhang, Zhu-ming; Goff, David C

2009-04-01

The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, chi(2), and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P<0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors (P<0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks.

Agroforestry systems and environmental quality: introduction.

PubMed

Nair, P K Ramachandran

2011-01-01

Investments in agroforestry research during the past three decades-albeit modest-have yielded significant gains in understanding the role of trees on farmlands, and the ecological and economic advantages of integrated farming systems. While early research focused mostly on farm or local levels, broader-level ecosystem services of agroforestry systems (AFS) have raised high expectations in recent years. The nine papers included in this special collection deal with three of such environmental benefits of AFS: water-quality enhancement, carbon sequestration, and soil improvement. These benefits are based on the perceived ability of (i) vegetative buffer strips (VBS) to reduce surface transport of agrochemical pollutants, (ii) large volumes of aboveground and belowground biomass of trees to store high amounts of C deeper in the soil profile, and (iii) trees to enhance soil productivity through biological nitrogen fixation, efficient nutrient cycling, and deep capture of nutrients. The papers included have, in general, substantiated these premises and provided new insights. For example, the riparian VBS are reported to increase the reservoir life, in addition to reducing transport of agrochemicals; the variations in C storage in different soil-fraction sizes suggest that microaggregate (250-53 μm) dynamics in the soil could be a good indicator of its C-storage potential; and the use of vector analysis technique is recommended in AFS to avoid consequences of inaccurate and overuse of fertilizers. The papers also identified significant knowledge gaps in these areas. A common theme across all three environmental quality issues covered is that more and varied research datasets across a broad spectrum of conditions need to be generated and integrated with powerful statistical tools to ensure wide applicability of the results. Furthermore, appropriate management practices that are acceptable to the targeted land users and agroforestry practitioners need to be designed to exploit these environmental benefits. The relative newness of research in environmental quality of AFS will pose some additional challenges as well. These include the lack of allometric equations for tree-biomass determination, absence of standardized norms on soil sampling depth, and limitations of fixed-effect models arising from issues such as pseudo-replication and repeated measures that are common in studies on preexisting field plots. Overall, this special collection is a timely effort in highlighting the promise of AFS in addressing some of the environmental quality issues, and the challenges in realizing that potential. American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.

Discriminating Talent Identified Junior Australian Footballers Using a Fundamental Gross Athletic Movement Assessment

PubMed Central

Woods, Carl T.; Banyard, Harry G.; McKeown, Ian; Fransen, Job; Robertson, Sam

2016-01-01

Talent identification (TID) is a pertinent component of the sports sciences, affording practitioners the opportunity to target developmental interventions to a select few; optimising financial investments. However, TID is multi-componential, requiring the recognition of immediate and prospective performance. The measurement of athletic movement skill may afford practitioners insight into the latter component given its augmented relationship with functional sport specific qualities. It is currently unknown whether athletic movement skill is a discriminant quality in junior Australian football (AF). This study aimed to discriminate talent identified junior AF players from their non-talent identified counterparts using a fundamental gross athletic movement assessment. From a total of 50 under 18 (U18) AF players; two groups were classified a priori based on selection level; talent identified (n = 25; state academy representatives) and non-talent identified (n = 25; state-based competition representatives). Players performed a fundamental gross athletic movement assessment based on the Athletic Ability Assessment (AAA), consisting of an overhead squat, double lunge (left and right legs), single leg Romanian deadlift (left and right legs), and a push up (six movement criterions). Movements were scored across three assessment points using a three-point scale (resulting in a possible score of nine for each movement). A multivariate analysis of variance revealed significant between group effects on four of the six movement criterions (d = 0.56 – 0.87; p = 0.01 – 0.02). Binary logistic regression models and a receiver operating characteristic curve inspection revealed that the overhead squat score provided the greatest group discrimination (β(SE) = -0.89(0.44); p < 0.05), with a score of 4.5 classifying 64% and 88% of the talent identified and non-talent identified groups, respectively. Results support the integration of this assessment into contemporary talent identification approaches in junior AF, as it may provide coaches with insight into a juniors developmental potential. Key points On average, talent identified junior AF players possess superior athletic movement qualities relative to their non-talent identified counterparts. The integration of this gross athletic movement assessment into contemporary multidimensional approaches to talent identification may enable insight into a juniors developmental potential. The athletic qualities underpinning the production of the overhead squat movement could augment functional physical qualities in junior Australian footballers. Assessing movement competency in junior contexts may afford practitioners with the opportunity to rectify inefficient fundamental movement patterns prior to entrance into elite senior ranks. PMID:27803635

Association of a Family History of Atrial Fibrillation With Incidence and Outcomes of Atrial Fibrillation: A Population-Based Family Cohort Study.

PubMed

Chang, Shang-Hung; Kuo, Chang-Fu; Chou, I-Jun; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Huang, Lu-Hsiang; Zhang, Weiya; Doherty, Michael; Wen, Ming-Shien; Kuo, Chi-Tai; Yeh, Yung-Hsin

2017-08-01

The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013. The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed. In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AF patients with vs without an affected first-degree relative had similar MACE-free survival. Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.

Common Atrial Fibrillation Risk Alleles at 4q25 Predict Recurrence after Catheter-based Atrial Fibrillation Ablation

PubMed Central

Shoemaker, M. Benjamin; Muhammad, Raafia; Parvez, Babar; White, Brenda W.; Streur, Megan; Song, Yanna; Stubblefield, Tanya; Kucera, Gayle; Blair, Marcia; Rytlewski, Jason; Parvathaneni, Sunthosh; Nagarakanti, Rangadham; Saavedra, Pablo; Ellis, Christopher; Whalen, S. Patrick; Roden, Dan M; Darbar, Dawood

2012-01-01

Background Common single nucleotide polymorphisms (SNPs) at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical AF. Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5–30% of AF cases. Objective To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. Methods Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years, 71% male, 89% typical AF) between 2004 and 2011. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF; [AT/AF]). Results Two-hundred AT/AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76 95% confidence interval [CI] 0.6–0.95, P=0.016) compared with wild-type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio = 0.79, 95% CI 0.62–0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio = 0.61, 95% CI 0.37–1.0) (P=0.037). Conclusion Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of predominately typical AF patients. Our findings suggest the rs2200733 polymorphism may hold promise as an as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation. PMID:23178686

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

Atrial Fibrillation Detection During 24-Hour Ambulatory Blood Pressure Monitoring: Comparison With 24-Hour Electrocardiography.

PubMed

Kollias, Anastasios; Destounis, Antonios; Kalogeropoulos, Petros; Kyriakoulis, Konstantinos G; Ntineri, Angeliki; Stergiou, George S

2018-07-01

This study assessed the diagnostic accuracy of a novel 24-hour ambulatory blood pressure (ABP) monitor (Microlife WatchBP O3 Afib) with implemented algorithm for automated atrial fibrillation (AF) detection during each ABP measurement. One hundred subjects (mean age 70.6±8.2 [SD] years; men 53%; hypertensives 85%; 17 with permanent AF; 4 paroxysmal AF; and 79 non-AF) had simultaneous 24-hour ABP monitoring and 24-hour Holter monitoring. Among a total of 6410 valid ABP readings, 1091 (17%) were taken in ECG AF rhythm. In reading-to-reading ABP analysis, the sensitivity, specificity, and accuracy of ABP monitoring in detecting AF were 93%, 87%, and 88%, respectively. In non-AF subjects, 12.8% of the 24-hour ABP readings indicated false-positive AF, of whom 27% were taken during supraventricular premature beats. There was a strong association between the proportion of false-positive AF readings and that of supraventricular premature beats ( r =0.67; P <0.001). Receiver operating characteristic curve revealed that in paroxysmal AF and non-AF subjects, AF-positive readings at 26% during 24-hour ABP monitoring had 100%/85% sensitivity/specificity (area under the curve 0.91; P <0.01) for detecting paroxysmal AF. These findings suggest that in elderly hypertensives, a novel 24-hour ABP monitor with AF detector has high sensitivity and moderate specificity for AF screening during routine ABP monitoring. Thus, in elderly hypertensives, a 24-hour ABP recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring. © 2018 American Heart Association, Inc.

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

PubMed

Massicotte-Azarniouch, David; Kuwornu, John Paul; Carrero, Juan-Jesus; Lam, Ngan N; Molnar, Amber O; Zimmerman, Deborah; McCallum, Megan K; Garg, Amit X; Sood, Manish M

2018-02-01

The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. Population-based retrospective cohort study from Ontario, Canada. 1,422,978 adult residents with eGFRs < 90mL/min/1.73m 2 from April 1, 2006, through March 31, 2015. A diagnosis of AF at hospitalization. Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m 2 . Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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 ...

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke.

PubMed

Bisson, Arnaud; Clementy, Nicolas; Bodin, Alexandre; Angoulvant, Denis; Babuty, Dominique; Lip, Gregory Y H; Fauchier, Laurent

2017-10-01

There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA 2 DS 2 -VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8-9.0). New AF patients had higher CHA 2 DS 2 -VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis. © 2017 American Heart Association, Inc.

Early, de novo atrial fibrillation after coronary artery bypass grafting: Facts and features.

PubMed

Yaksh, Ameeta; Kik, Charles; Knops, Paul; van Ettinger, Maarten J B; Bogers, Ad J J C; de Groot, Natasja M S

2017-02-01

Knowledge of the mechanism underlying post-operative atrial fibrillation (PoAF) is essential for development of preventive measures. The incidence and characteristics of both PoAF and supraventricular premature beats triggering PoAF, their interrelationship and alterations over time have never been examined. The goal of this study is therefore to examine the correlation between the incidence and characteristics of supraventricular premature beats (SVPBs) and PoAF episodes in patients undergoing CABG in the first five post-operative days. PoAF episodes (N=327) and SVPBs (N=141,873) were characterized in 29 patients (63±9 years; 22 (76%) male) undergoing coronary artery bypass grafting and compared with a control group of patients without PoAF by using continuous cardiac rhythm monitoring during the first 5 days after surgery. Most patients (N=18, 62%) had multiple PoAF episodes; the median number of PoAF episodes per patient was 3 and varied between 1 and 139. The majority of PoAF episodes developed on the second and third post-operative day (55%). The averaged median duration of PoAF episodes per patient was 469±1085 min. Patients with PoAF had a higher SVPBs burden compared to subjects without PoAF (0.9% vs 0.2%, P<.001). SVPBs initiating PoAF had shorter coupling intervals than SVPBs which did not initiate PoAF episodes (58% vs 64% (P<.001) and were preceded by heart rate acceleration. PoAF episodes are mainly repetitive though transient in nature. There was a considerable inter-individual variation in both AF and SVPB characteristics, despite a similar underlying clinical profile. The SVPB burden is higher in patients with PoAF and the mode of onset is characterized by short coupled SVPBs. Determination of individual post-operative dysrhythmia profiles enables identification of patients at risk for developing PoAF. Copyright © 2016 Elsevier Inc. All rights reserved.

Is HATCH score a reliable predictor of atrial fibrillation after cavotricuspid isthmus ablation for typical atrial flutter?

PubMed

García-Seara, Javier; Gude Sampedro, Francisco; Martínez Sande, Jose L; Fernández López, Xesus Alberte; Rodríguez Mañero, Moisés; González Melchor, Laila; Alvarez Alvarez, Belén; Iglesias Alvarez, Diego; González Juanatey, José Ramón

2016-09-01

We determined the effectiveness of the HATCH score in patients with typical atrial flutter (AFl) undergoing cavotricuspid isthmus (CTI) ablation to predict long-term atrial fibrillation (AF). We conducted an observational retrospective single-center cohort study including all patients admitted to our hospital for a CTI ablation between 1998 and 2010. The patients were divided into four categories: 1) new-onset AF (no prior AF and AF during follow-up (FU)); 2) old AF (prior AF and no AF during FU); 3) prior and post AF (AF prior and post CTI ablation); and 4) no AF. Four hundred and eight patients were included. In patients without prior AF, the hazard ratio (HR) for new-onset AF during FU was 0.98 (CI 95%: 0.65-1.50; p = 0.95) and 1.00 (CI 95%: 0.57-1.77; p = 0.98) for HATCH ≥ 2 and HATCH ≥ 3, respectively. In patients with prior AF, the HR for AF was 1.41 (CI 95%: 0.87-2.28; p = 0.17) and 1.79 (CI 95%: 0.96-3.35; p = 0.06), for HATCH ≥ 2 and HATCH ≥ 3, respectively. Left atrial enlargement was positively correlated with the occurrence of AF during FU, especially in the subgroup without prior AF, which had a HR of 2.44 (CI 95%: 1.35-4.40; p = 0.003), a HR of 2.88 (CI 95%: 1.36-6.10; p = 0.006) and a HR of 3.68 (CI 95%: 1.71-7.94; p = 0.001), for slight, moderate and severely dilated left atrial dimension, respectively, compared with a normal value. HATCH score did not predict AF in patients with typical AFl who underwent CTI ablation. Basal left atrium dimension could help predict new-onset AF.

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

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

Installation Restoration Program. Phase 1 - Records Search AAC-Northern Region, Galena AFS, Campion AFS, Cape Lisburne AFS, Fort Yukon AFS, Indian Mountain AFS, Kotzebue AFS, Murphy Dome AFS, and Tin City AFS

DTIC Science & Technology

1985-09-01

GM SILTY GRAVEL GP POORLY GRADED GRAVEL SM SILTY SAND SP POORLY GRADED SAND SW WELL GRADED SAND ML LOW PLASTICITY SILT SOURCE: INSTALLATION DOCUMENTS... plastic on the side toward th’e beach in an attempt to prevent migration of fuel. to the beach. During the site visit for this Phase I IRP study the...Force have included garbage, refuse, incinerator ash (since 1975), wood, metal, plastic and bulky - materials such as construction and demolition debris

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis.

PubMed

Kanthan, Senthooran Kathirgama; Bush, Andrew; Kemp, Michael; Buchdahl, Roger

2007-09-01

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function. (c) 2007 Wiley-Liss, Inc.

Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.

PubMed

Oba, Kageyuki; Maeda, Minetaka; Maimaituxun, Gulinu; Yamaguchi, Satoshi; Arasaki, Osamu; Fukuda, Daiju; Yagi, Shusuke; Hirata, Yukina; Nishio, Susumu; Iwase, Takashi; Takao, Shoichiro; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Harada, Masafumi; Masuzaki, Hiroaki; Sata, Masataka; Shimabukuro, Michio

2018-05-25

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m 2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m 2 , P<0.01). The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Maximizing Performance: Augmented Feedback, Focus of Attention, and/or Reward?

PubMed

Wälchli, Michael; Ruffieux, Jan; Bourquin, Yann; Keller, Martin; Taube, Wolfgang

2016-04-01

Different approaches like providing augmented feedback (aF), applying an external focus of attention (EF), or rewarding participants with money (RE) have been shown to instantly enhance motor performance. So far, these approaches have been tested either in separate studies or directly against each other. However, there is no study that combined aF, EF, and/or RE to test whether this provokes additional benefits. The aim of the present study was therefore to identify the most powerful combination. Eighteen participants performed maximal countermovement jumps in six different conditions: neutral (NE), aF, RE, aF + EF, aF + RE, and aF + EF + RE. Participants demonstrated the highest jump heights with aF + EF, followed by aF + EF + RE, aF + RE, aF, RE, and finally, NE. Activity of the M. rectus femoris differed significantly between conditions resulting in lower muscular activity in aF + EF and aF + EF + RE compared with NE. All other parameters, such as ground reaction forces and joint angles, were comparable across conditions. This is the first study showing superior performance when combining aF with EF. As reduced muscular activity was found only in conditions with EF, it is argued in line with the constrained action hypothesis that adopting an EF improves movement efficiency. In contrast, aF seems to rather enhance (intrinsic) motivation. However, monetary reward did not further amplify performance.

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.

Ethnic Distribution of ECG Predictors of Atrial Fibrillation and Its Impact on Understanding the Ethnic Distribution of Ischemic Stroke in the Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Soliman, Elsayed Z.; Prineas, Ronald J.; Case, L. Douglas; Zhang, Zhu-ming; Goff, David C.

2009-01-01

Background and Purpose The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. Methods The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, χ2, and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. Results Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P<0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors (P<0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. Conclusions There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks. PMID:19213946

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

Mechanisms for achieving adolescent-friendly services in Ecuador: a realist evaluation approach

PubMed Central

Goicolea, Isabel; Coe, Anna-Britt; Hurtig, Anna-Karin; San Sebastian, Miguel

2012-01-01

Background Despite evidence showing that adolescent-friendly health services (AFSs) increase young people's access to these services, health systems across the world are failing to integrate this approach. In Latin America, policies aimed at strengthening AFS abound. However, such services are offered only in a limited number of sites, and providers’ attitudes and respect for confidentiality have not been addressed to a sufficient extent. Methods The aim of this study was to explore the mechanisms that triggered the transformation of an ‘ordinary’ health care facility into an AFS in Ecuador. For this purpose, a realist evaluation approach was used in order to analyse three well-functioning AFSs. Information was gathered at the national level and from each of the settings including: (i) statistical information and unpublished reports; (ii) in-depth interviews and focus group discussions with policy makers, health care providers, users and adolescents participating in youth organisations and (iii) observations at the health care facilities. Thematic analysis was carried out, driven by the realist evaluation approach, namely exploring the connections between mechanisms, contexts and outcomes. Results The results highlighted that the development of the AFSs was mediated by four mechanisms: grounded self-confidence in trying new things, legitimacy, a transformative process and an integral approach to adolescents. Along this process, contextual factors at the national and institutional levels were further explored. Conclusion The Ministry of Health of Ecuador, based on the New Guidelines for Comprehensive Care of Adolescent Health, has started the scaling up of AFSs. Our research points towards the need to recognise and incorporate these mechanisms as part of the implementation strategy from the very beginning of the process. Although contextually limited to Ecuador, many mechanisms and good practices in these AFS may be relevant to the Latin American setting and elsewhere. PMID:22855646

Silent Atrial Fibrillation in Elderly Pacemaker Users: A Randomized Trial Using Home Monitoring.

PubMed

Lima, Ceb; Martinelli, M; Peixoto, G L; Siqueira, S F; Wajngarten, Maurício; Silva, Rodrigo Tavares; Costa, Roberto; Filho, Roberto; Ramires, José Antônio Franchini

2016-05-01

Pacemaker with remote monitoring (PRM) may be useful for silent atrial fibrillation (AF) detection. The aims of this study were to evaluate the incidence of silent AF, the role of PRM, and to determine predictors of silent AF occurrence. Three hundred elderly patients with permanent pacemaker (PPM) were randomly assigned to the remote group (RG) or control group (CG). All patients received PPM with remote monitoring capabilities. Primary end point was AF occurrence rate and the secondary end points were time to AF detection and number of days with AF. During the average follow-up of 15.7±7.7 months, AF episodes were detected in 21.6% (RG = 24% vs CG = 19.3%, P = 0.36]. There was no difference in the time to detect the first AF episode. However, the median time to detect AF recurrence in the RG was lower than that in the CG (54 days vs 100 days, P = 0.004). The average number of days with AF was 16.0 and 51.2 in the RG and CG, respectively (P = 0.028). Predictors of silent AF were left atrial diameter (odds ratio [OR] 1.2; 95% CI = 1.1-1.3; P < 0.001) and diastolic dysfunction (OR 4.8; 95% CI = 1.6-14.0; P = 0.005). The incidence of silent AF is high in elderly patients with pacemaker; left atrial diameter and diastolic dysfunction were predictors of its occurrence. AF monitoring by means of pacemaker is a valuable tool for silent AF detection and continuous remote monitoring allows early AF recurrence detection and reduces the number of days with AF. © 2015 Wiley Periodicals, Inc.

Association of Left Atrial Function Index With Late Atrial Fibrillation Recurrence after Catheter Ablation.

PubMed

Sardana, Mayank; Ogunsua, Adedotun A; Spring, Matthew; Shaikh, Amir; Asamoah, Owusu; Stokken, Glenn; Browning, Clifford; Ennis, Cynthia; Donahue, J Kevin; Rosenthal, Lawrence S; Floyd, Kevin C; Aurigemma, Gerard P; Parikh, Nisha I; McManus, David D

2016-12-01

Although catheter ablation (CA) for atrial fibrillation (AF) is commonly used to improve symptoms, AF recurrence is common and new tools are needed to better inform patient selection for CA. Left atrial function index (LAFI), an echocardiographic measure of atrial mechanical function, has shown promise as a noninvasive predictor of AF. We hypothesized that LAFI would relate to AF recurrence after CA. All AF patients undergoing index CA were enrolled in a prospective institutional AF Treatment Registry between 2011 and 2014. LAFI was measured post hoc from pre-ablation clinical echocardiographic images in 168 participants. Participants were mostly male (33% female), middle-aged (60 ± 10 years), obese and had paroxysmal AF (64%). Mean LAFI was 25.9 ± 17.6. Over 12 months of follow-up, 78 participants (46%) experienced a late AF recurrence. In logistic regression analyses adjusting for factors known to be associated with AF, lower LAFI remained associated with AF recurrence after CA [OR 0.04 (0.01-0.67), P = 0.02]. LAFI discriminated AF recurrence after CA slightly better than CHADS2 (C-statistic 0.60 LAFI, 0.57 CHADS2). For participants with persistent AF, LAFI performed significantly better than CHADS2 score (C statistic = 0.79 LAFI, 0.56 CHADS2, P = 0.02). LAFI, an echocardiographic measure of atrial function, is associated with AF recurrence after CA and has improved ability to discriminate AF recurrence as compared to the CHADS-2 score, especially among persistent AF patients. Since LAFI can be calculated using standard 2D echocardiographic images, it may be a helpful tool for predicting AF recurrence. © 2016 Wiley Periodicals, Inc.

DISCORDANCE BETWEEN BLUE-LIGHT AUTOFLUORESCENCE AND NEAR-INFRARED AUTOFLUORESCENCE IN AGE-RELATED MACULAR DEGENERATION.

PubMed

Heiferman, Michael J; Fawzi, Amani A

2016-12-01

To identify the origin and significance of discordance between blue-light autofluorescence (BL-AF; 488 nm) and near-infrared autofluorescence (NI-AF; 787 nm) in patients with age-related macular degeneration (AMD). A total of 86 eyes of 59 patients with a diagnosis of AMD were included in this cross-sectional study conducted between March 9, 2015 and May 1, 2015. A masked observer examined the BL-AF, NI-AF, and spectral-domain optical coherence tomography images. Areas with discordance of autofluorescence patterns between NI-AF and BL-AF images were correlated with structural findings at the corresponding location in optical coherence tomography scans. Seventy-nine eyes had discordance between BL-AF and NI-AF. The most common optical coherence tomography finding accounting for these discrepancies was pigment migration accounting for 35 lesions in 21 eyes. The most clinically relevant finding was geographic atrophy missed on BL-AF in 7 eyes. Our findings indicate that variations in the distribution of lipofuscin, melanin and melanolipofuscin account for the majority of discordance between BL-AF and NI-AF. Given our finding of missed geographic atrophy lesions on BL-AF in 24% of eyes with geographic atrophy (7/29 eyes), clinicians should consider multimodal imaging, including NI-AF and optical coherence tomography, especially in clinical trials of geographic atrophy.

Discordance between Blue-Light Autofluorescence and Near-Infrared Autofluorescence in Age-Related Macular Degeneration

PubMed Central

Heiferman, Michael J.; Fawzi, Amani A.

2016-01-01

Purpose To identify the origin and significance of discordance between blue-light autofluorescence (BL-AF; 488nm) and near-infrared autofluorescence (NI-AF; 787nm) in patients with age-related macular degeneration (AMD). Methods A total of 86 eyes of 59 patients with a diagnosis of AMD were included in this cross-sectional study conducted between March 9, 2015 and May 1, 2015. A masked observer examined the BL-AF, NI-AF, and spectral-domain optical coherence tomography (OCT) images. Areas with discordance of autofluorescence patterns between NI-AF and BL-AF images were correlated with structural findings at the corresponding location in OCT scans. Results 79 eyes had discordance between BL-AF and NI-AF. The most common OCT finding accounting for these discrepancies was pigment migration accounting for 35 lesions in 21 eyes. The most clinically relevant finding was geographic atrophy missed on BL-AF in seven eyes. Conclusions Our findings indicate that variations in the distribution of lipofuscin, melanin and melanolipofuscin account for the majority of discordance between BL-AF and NI-AF. Given our finding of missed geographic atrophy lesions on BL-AF in 24% of eyes with geographic atrophy (7/29 eyes), clinicians should consider multimodal imaging, including NI-AF and OCT, especially in clinical trials of geographic atrophy. PMID:28005672

Feasibility and Usability of a Mobile Application to Assess Symptoms and Affect in Patients with Atrial Fibrillation: A Pilot Study.

PubMed

Ghanbari, Hamid; Ansari, Sardar; Ghannam, Michael; Lathkar-Pradhan, Sangeeta; Kratz, Anna; Oral, Hakan; Najarian, Kayvan; Clauw, Daniel; Nallamothu, Brahmajee

2017-01-01

Atrial fibrillation (AF) is the most prevalent arrhythmia leading to hospital admissions. The majority of patients with AF report symptoms that are believed to be associated with the arrhythmia. The symptoms related to AF traditionally are collected during a clinic visit that is influenced by biases associated with recalling the experience over a limited period of time. We designed this pilot study to assess the usability and feasibility of a mobile application to assess symptoms in patients with AF. We designed a mobile application (miAfib) to assess symptoms (chest pain, palpitation, shortness of breath, fatigue, dizziness/lightheadedness), positive affect (happy, excited, content) and negative affect (worried, angry, sad) on multiple occasions throughout the day based on iOS platform. We performed a four-week feasibility trial to examine user adherence, acceptance and experiences with the mobile application. We administered questionnaires to assess factors affecting usage and self-reported acceptance of the application based on a five-point Likert scale with zero representing strongly disagree and 5 representing strongly disagree with. We included ten patients with paroxysmal and persistent AF. The mean number of completed assessments each day was 2.81 ± 1.59 with 94.7% of days with at least one assessment. The users found the application easy to use (4.75±0.46), intended to use it in the future (4.37±1.06) and found it easy to integrate into daily routine (4.5±1.07). In this pilot study, we found participants in this four-week trial reliably used the application and were able to use the app to report their daily symptoms and affect regularly. Participants reported that they found the application easy to use and would consider using the application in the future.

Prediction of new-onset atrial fibrillation after first-ever ischemic stroke: A comparison of CHADS2, CHA2DS2-VASc and HATCH scores and the added value of stroke severity.

PubMed

Hsieh, Cheng-Yang; Lee, Cheng-Han; Wu, Darren Philbert; Sung, Sheng-Feng

2018-05-01

Early detection of atrial fibrillation after stroke is important for secondary prevention in stroke patients without known atrial fibrillation (AF). We aimed to compare the performance of CHADS 2 , CHA 2 DS 2 -VASc and HATCH scores in predicting AF detected after stroke (AFDAS) and to test whether adding stroke severity to the risk scores improves predictive performance. Adult patients with first ischemic stroke event but without a prior history of AF were retrieved from a nationwide population-based database. We compared C-statistics of CHADS 2 , CHA 2 DS 2 -VASc and HATCH scores for predicting the occurrence of AFDAS during stroke admission (cohort I) and during follow-up after hospital discharge (cohort II). The added value of stroke severity to prediction models was evaluated using C-statistics, net reclassification improvement, and integrated discrimination improvement. Cohort I comprised 13,878 patients and cohort II comprised 12,567 patients. Among them, 806 (5.8%) and 657 (5.2%) were diagnosed with AF, respectively. The CHADS 2 score had the lowest C-statistics (0.558 in cohort I and 0.597 in cohort II), whereas the CHA 2 DS 2 -VASc score had comparable C-statistics (0.603 and 0.644) to the HATCH score (0.612 and 0.653) in predicting AFDAS. Adding stroke severity to each of the three risk scores significantly increased the model performance. In stroke patients without known AF, all three risk scores predicted AFDAS during admission and follow-up, but with suboptimal discrimination. Adding stroke severity improved their predictive abilities. These risk scores, when combined with stroke severity, may help prioritize patients for continuous cardiac monitoring in daily practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential baroreflex control of heart rate in sedentary and aerobically fit individuals

NASA Technical Reports Server (NTRS)

Smith, S. A.; Querry, R. G.; Fadel, P. J.; Welch-O'Connor, R. M.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

2000-01-01

PURPOSE: We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy young adults. METHODS: Arterial and aortic (ABR) baroreflex functions were assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively. Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of both pressure and suction delivered to the carotid sinus via a neck chamber collar, independent of drug administration. RESULTS: During vasoactive drug injection, mean arterial pressure (MAP) was similarly altered in average fit (AF) and high fit (HF) groups. However, the heart rate (HR) response range of the arterial baroreflex was significantly attenuated (P < 0.05) in HF (31+/-4 beats x min(-1)) compared with AF individuals (46+/-4 beats x min(-1)). When sustained neck suction and pressure were applied to counteract altered carotid sinus pressure during SN and PE administration, isolating the ABR response, the response range remained diminished (P < 0.05) in the HF population (24+/-3 beats x min(-1)) compared with the AF group (41+/-4 beats x min(-1)). During CBR perturbation, the HF (14+/-1 beats-min(-1)) and AF (16+/-1 beats-min(-1)) response ranges were similar. The arterial baroreflex response range was significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS: These data confirm that reductions in arterial-cardiac reflex sensitivity are mediated by diminished ABR function. More importantly, these data suggest that the integrative relationship between the ABR and CBR contributing to arterial baroreflex control of HR is inhibitory in nature and not altered by exercise training.

Integrating Genetic, Transcriptional, and Functional Analyses to Identify Five Novel Genes for Atrial Fibrillation

PubMed Central

Sinner, Moritz F.; Tucker, Nathan R.; Lunetta, Kathryn L.; Ozaki, Kouichi; Smith, J. Gustav; Trompet, Stella; Bis, Joshua C.; Lin, Honghuang; Chung, Mina K.; Nielsen, Jonas B.; Lubitz, Steven A.; Krijthe, Bouwe P.; Magnani, Jared W.; Ye, Jiangchuan; Gollob, Michael H.; Tsunoda, Tatsuhiko; Müller-Nurasyid, Martina; Lichtner, Peter; Peters, Annette; Dolmatova, Elena; Kubo, Michiaki; Smith, Jonathan D.; Psaty, Bruce M.; Smith, Nicholas L.; Jukema, J. Wouter; Chasman, Daniel I.; Albert, Christine M.; Ebana, Yusuke; Furukawa, Tetsushi; MacFarlane, Peter; Harris, Tamara B.; Darbar, Dawood; Dörr, Marcus; Holst, Anders G.; Svendsen, Jesper H.; Hofman, Albert; Uitterlinden, Andre G.; Gudnason, Vilmundur; Isobe, Mitsuaki; Malik, Rainer; Dichgans, Martin; Rosand, Jonathan; Van Wagoner, David R.; Benjamin, Emelia J.; Milan, David J.; Melander, Olle; Heckbert, Susan R.; Ford, Ian; Liu, Yongmei; Barnard, John; Olesen, Morten S.; Stricker, Bruno H.C.; Tanaka, Toshihiro; Kääb, Stefan; Ellinor, Patrick T.

2014-01-01

Background Atrial fibrillation (AF) affects over 30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. Methods & Results To identify new AF-related genes, we utilized a multifaceted approach, combining large-scale genotyping in two ethnically distinct populations, cis-eQTL mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501, RR=1.18, 95%CI 1.13 – 1.23, p=6.5×10−16), GJA1 (rs13216675, RR=1.10, 95%CI 1.06 – 1.14, p=2.2×10−8), TBX5 (rs10507248, RR=1.12, 95%CI 1.08 – 1.16, p=5.7×10−11), and CAND2 (rs4642101, RR=1.10, 95%CI 1.06 – 1.14, p=9.8×10−9). In Japanese, novel loci were identified near NEURL (rs6584555, RR=1.32, 95%CI 1.26–1.39, p=2.0×10−25) and CUX2 (rs6490029, RR=1.12, 95%CI 1.08–1.16, p=3.9×10−9). The top SNPs or their proxies were identified as cis-eQTLs for the genes CAND2 (p=2.6×10−19), GJA1 (p=2.66×10−6), and TBX5 (p=1.36×10−05). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). Conclusions We have identified five novel loci for AF. Our results further expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation. PMID:25124494

Recalibration of the earthworm tier 1 risk assessment of plant protection products.

PubMed

Christl, Heino; Bendall, Julie; Bergtold, Matthias; Coulson, Mike; Dinter, Axel; Garlej, Barbara; Hammel, Klaus; Kabouw, Patrick; Sharples, Amanda; von Mérey, Georg; Vrbka, Silvie; Ernst, Gregor

2016-10-01

In the first step of earthworm risk assessment for plant protection products (PPPs), the risk is assessed by comparing the no-observed effect levels (NOELs) from laboratory reproduction tests with the predicted exposure of the PPP in soil, while applying a trigger value (assessment factor [AF]) to cover uncertainties. If this step indicates a potential risk, field studies are conducted. However, the predicted environmental concentration in soil, which can be calculated, for example, for different soil layers (ranging from 0-1 cm to 0-20 cm), and the AF determine the conservatism that is applied in this first step. In this review paper, the tier 1 earthworm risk assessment for PPPs is calibrated by comparing the NOEL in earthworm reproduction tests with effect levels on earthworm populations under realistic field conditions. A data set of 54 pairs of studies conducted in the laboratory and in the field with the same PPP was compiled, allowing a direct comparison of relevant endpoints. The results indicate that a tier 1 AF of 5 combined with a regulatory relevant soil layer of 0 to 5 cm provides a conservative tier 1 risk assessment. A risk was identified by the tier 1 risk assessment in the majority of the cases at application rates that were of low risk for natural earthworm populations under field conditions. Increasing the conservatism in the tier 1 risk assessment by reducing the depth of the regulatory relevant soil layer or by increasing the tier 1 AF would increase the number of false positives and trigger a large number of additional field studies. This increased conservatism, however, would not increase the margin of safety for earthworm populations. The analysis revealed that the risk assessment is conservative if an AF of 5 and a regulatory relevant soil layer of 0 to 5 cm is used. Integr Environ Assess Manag 2016;12:643-650. © 2015 SETAC. © 2015 SETAC.

A QoS scheme for a congestion core network based on dissimilar QoS structures in smart-phone environments.

PubMed

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones.

A QoS Scheme for a Congestion Core Network Based on Dissimilar QoS Structures in Smart-Phone Environments

PubMed Central

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones. PMID:22163453

Performance and age of African and non-African runners in half- and full marathons held in Switzerland, 2000–2010

PubMed Central

Aschmann, André; Knechtle, Beat; Cribari, Marco; Rüst, Christoph Alexander; Onywera, Vincent; Rosemann, Thomas; Lepers, Romuald

2013-01-01

Background Endurance running performance of African (AF) and non-African (NAF) athletes is investigated, with better performances seen for Africans. To date, no study has compared the age of peak performance between AF and NAF runners. The present research is an analysis of the age and running performance of top AF and NAF athletes, using the hypothesis that AF athletes were younger and faster than NAF athletes. Methods Age and performance of male and female AF and NAF athletes in half-marathons and marathons held in Switzerland in 2000–2010 were investigated using single and multilevel hierarchical regression analyses. Results For half-marathons, male NAF runners were older than male AF runners (P = 0.02; NAF, 31.1 years ± 6.4 years versus AF, 26.2 years ± 4.9 years), and their running time was longer (P = 0.02; NAF, 65.3 minutes ± 1.7 minutes versus AF, 64.1 minutes ± 0.9 minutes). In marathons, differences between NAF and AF male runners in age (NAF, 33.0 years ± 4.8 years versus AF, 28.6 years ± 3.8 years; P < 0.01) and running time (NAF, 139.5 minutes ± 5.6 minutes versus AF, 133.3 minutes ± 2.7 minutes; P < 0.01) were more pronounced. There was no difference in age (NAF, 31.0 years ± 7.0 years versus AF, 26.7 years ± 6.0 years; P > 0.05) or running time (NAF, 75.0 minutes ± 3.7 minutes versus AF, 75.6 minutes ± 5.3 minutes; P > 0.05) between NAF and AF female half-marathoners. For marathoners, NAF women were older than AF female runners (P = 0.03; NAF, 31.6 years ± 4.8 years versus AF, 27.8 years ± 5.3 years), but their running times were similar (NAF, 162.4 minutes ± 7.2 minutes versus AF, 163.0 minutes ± 7.0 minutes; P > 0.05). Conclusion In Switzerland, the best AF male half-marathoners and marathoners were younger and faster than the NAF counterpart runners. In contrast to the results seen in men, AF and NAF female runners had similar performances. Future studies need to investigate performance and age of AF and NAF marathoners in the World Marathon Majors Series. PMID:24379724

Estrogen Receptor α L543A,L544A Mutation Changes Antagonists to Agonists, Correlating with the Ligand Binding Domain Dimerization Associated with DNA Binding Activity*

PubMed Central

Arao, Yukitomo; Hamilton, Katherine J.; Coons, Laurel A.; Korach, Kenneth S.

2013-01-01

A ligand-dependent nuclear transcription factor, ERα has two transactivating functional domains (AF), AF-1 and AF-2. AF-1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding domain (LBD) of the ERα protein. Helix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible to an active or inactive form. We demonstrated previously that the ERα mutant (AF2ER) possessing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestrant/ICI182780 (ICI) or 4-hydoxytamoxifen (OHT) into agonists in the AF2ER knock-in mouse. Our previous in vitro studies suggested that the mode of AF2ER activation is similar to the partial agonist activity of OHT for WT-ERα. However, it is still unclear how antagonists activate ERα. To understand the molecular mechanism of antagonist reversal activity, we analyzed the correlation between the ICI-dependent estrogen-responsive element-mediated transcription activity of AF2ER and AF2ER-LBD dimerization activity. We report here that ICI-dependent AF2ER activation correlated with the activity of AF2ER-LBD homodimerization. Prevention of dimerization impaired the ICI-dependent ERE binding and transcription activity of AF2ER. The dislocation of H12 caused ICI-dependent LBD homodimerization involving the F-domain, the adjoining region of H12. Furthermore, F-domain truncation also strongly depressed the dimerization of WT-ERα-LBD with antagonists but not with E2. AF2ER activation levels with ICI, OHT, and raloxifene were parallel with the degree of AF2ER-LBD homodimerization, supporting a mechanism that antagonist-dependent LBD homodimerization involving the F-domain results in antagonist reversal activity of H12-mutated ERα. PMID:23733188

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.

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.

Integrated Defense: Lessons Learned from Joint Base Balad

DTIC Science & Technology

2013-01-01

Fall 2004): 65–74. http://www.airpower.au.af.mil/airchronicles /apj/apj04/fal04/Fal04.pdf. Butterfield, SSgt Phillip . “Iraqi Army Returns to Joint...PhD Air University Press Team Chief Editor Jerry L. Gantt Copy Editor Sherry Terrell Cover Art and Book Design Daniel Armstrong Composition and Prepress Production Nedra Looney Print Preparation and Distribution Diane Clark

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

Koshelev, A. E.

Multiple-band electronic structure and proximity to antiferromagnetic (AF) instability are the key properties of iron-based superconductors. In this paper, we explore the influence of scattering by the AF spin fluctuations on transport of multiple-band metals above the magnetic transition. A salient feature of scattering on the AF fluctuations is that it is strongly enhanced at the Fermi surface locations where the nesting is perfect (“hot spots” or “hot lines”). We review derivation of the collision integral for the Boltzmann equation due to AF-fluctuations scattering. In the paramagnetic state, the enhanced scattering rate near the hot lines leads to anomalous behaviormore » of electronic transport in magnetic field. We explore this behavior by analytically solving the Boltzmann transport equation with approximate transition rates. This approach accounts for return scattering events and is more accurate than the relaxation-time approximation. The magnetic-field dependences are characterized by two very different field scales: the lower scale is set by the hot-spot width and the higher scale is set by the total scattering amplitude. A conventional magnetotransport behavior is limited to magnetic fields below the lower scale. In the wide range in-between these two scales, the longitudinal conductivity has linear dependence on the magnetic field and the Hall conductivity has quadratic dependence. The linear dependence of the diagonal component reflects growth of the Fermi-surface area affected by the hot spots proportional to the magnetic field. Finally, we discuss applicability of this theoretical framework for describing of anomalous magnetotransport properties in different iron pnictides and chalcogenides in the paramagnetic state.« less

Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study.

PubMed

Lubitz, Steven A; Yin, Xiaoyan; McManus, David D; Weng, Lu-Chen; Aparicio, Hugo J; Walkey, Allan J; Rafael Romero, Jose; Kase, Carlos S; Ellinor, Patrick T; Wolf, Philip A; Seshadri, Sudha; Benjamin, Emelia J

2017-02-01

To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF. © 2017 American Heart Association, 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.

Protective effects of Urtica dioica seed extract in aflatoxicosis: histopathological and biochemical findings.

PubMed

Uyar, A; Yener, Z; Dogan, A

2016-04-01

The ameliorative potential and antioxidant capacity of an extract of Urtica dioica seeds (UDS) was investigated using histopathological changes in liver and kidney, measuring serum marker enzymes, antioxidant defence systems and lipid peroxidation (malondialdehyde (MDA)) content in various tissues of broilers exposed to aflatoxin (AF). A total of 32 broilers were divided randomly into 4 groups: control, UDS extract-treated, AF-treated and AF+UDS extract-treated. Broilers in control and UDS extract-treated groups were fed on a diet without AF. The AF-treated group and AF+UDS extract-treated groups were treated with an estimated 1 mg total AF/kg feed. The AF+UDS extract groups received in addition 30 ml UDS extract/kg diet for 21 d. The AF-treated group had significantly decreased body weight gain when compared to the other groups. Biochemical analysis showed a small increase in the concentrations of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and lactate dehydrogenase in the AF-treated group compared to that of the control group, whereas concentrations of these enzymes were decreased in the AF+UDS group compared to that of the AF-treated group. Administration of supplementary UDS extract helped restore the AF-induced increase in MDA and reduced the antioxidant system towards normality, particularly in the liver, brain, kidney and heart. Hepatorenal protection by UDS extracts was further supported by the almost normal histology in AF+UDS extract-treated group as compared to the degenerative changes in the AF-treated broilers. It was concluded that UDS extract has a protective hepatorenal effect in broilers affected by aflatoxicosis, probably acting by promoting the antioxidative defence systems.

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.

Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators.

PubMed

Hart, R G; Pearce, L A; Rothbart, R M; McAnulty, J H; Asinger, R W; Halperin, J L

2000-01-01

This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation (AF). Although intermittent AF is common, relatively little is known about the attendant risk of stroke. A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis. Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%). In patients with intermittent AF, independent predictors of ischemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% confidence interval 4.5 to 14). In this large cohort of AF patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors. Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation. High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF.

Clinical predictors of risk for atrial fibrillation: implications for diagnosis and monitoring.

PubMed

Brunner, Kyle J; Bunch, T Jared; Mullin, Christopher M; May, Heidi T; Bair, Tami L; Elliot, David W; Anderson, Jeffrey L; Mahapatra, Srijoy

2014-11-01

To create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF). The AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA2DS2-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis. A total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820). We developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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.

Targeting Stable Rotors to Treat Atrial Fibrillation.

PubMed

Narayan, Sanjiv M; Krummen, David E

2012-09-01

Therapy for atrial fibrillation (AF) remains suboptimal, in large part because its mechanisms are unclear. While pulmonary vein ectopy may trigger AF, it remains uncertain how AF, once triggered, is actually sustained. Recent discoveries show that human AF is maintained by a small number of rotors or focal sources. AF sources are widely distributed in patient-specific locations, often remote from pulmonary veins and in the right atrium and stable for prolonged periods of time. In a multicentre experience, brief targeted ablation at sources (focal impulse and rotor modulation [FIRM]) terminated AF predominantly to sinus rhythm prior to pulmonary vein isolation and eliminated AF on rigorous followup. This review summarises the evidence for stable rotors and focal sources of human AF and their clinical role as ablation targets to eliminate paroxysmal, persistent and long-standing persistent AF.

Obstructive Sleep Apnoea and Atrial Fibrillation

PubMed Central

Zhang, Ling; Hou, Yuemei; Po, Sunny S

2015-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with significant morbidity and mortality. Obstructive sleep apnoea (OSA) is common among patients with AF. Growing evidence suggests that OSA is associated with the initiation and maintenance of AF. This association is independent of obesity, body mass index and hypertension. OSA not only promotes initiation of AF but also has a significant negative impact on the treatment of AF. Patients with untreated OSA have a higher AF recurrence rate with drug therapy, electrical cardioversion and catheter ablation. Treatment with continuous positive airway pressure (CPAP) has been shown to improve AF control in patients with OSA. In this article, we will review and discuss the pathophysiological mechanisms of OSA that may predispose OSA patients to AF as well as the standard and emerging therapies for patients with both OSA and AF. PMID:26835094

Genetic Risk Prediction of Atrial Fibrillation

PubMed Central

Lubitz, Steven A.; Yin, Xiaoyan; Lin, Henry J.; Kolek, Matthew; Smith, J. Gustav; Trompet, Stella; Rienstra, Michiel; Rost, Natalia S.; Teixeira, Pedro L.; Almgren, Peter; Anderson, Christopher D.; Chen, Lin Y.; Engström, Gunnar; Ford, Ian; Furie, Karen L.; Guo, Xiuqing; Larson, Martin G.; Lunetta, Kathryn L.; Macfarlane, Peter W.; Psaty, Bruce M.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Stott, David J.; Taylor, Kent D.; Weng, Lu-Chen; Yao, Jie; Geelhoed, Bastiaan; Verweij, Niek; Siland, Joylene E.; Kathiresan, Sekar; Roselli, Carolina; Roden, Dan; van der Harst, Pim; Darbar, Dawood; Jukema, J. Wouter; Melander, Olle; Rosand, Jonathan; Rotter, Jerome I.; Heckbert, Susan R.; Ellinor, Patrick T.; Alonso, Alvaro; Benjamin, Emelia J.

2017-01-01

Background Atrial fibrillation (AF) is common and has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 controls. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1×10−3 to <1×10−8 in a prior independent genetic association study. Results Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13–1.46; P=1.5×10−4) to 1.67 (25 variants; 95%CI, 1.47–1.90; P=9.3×10−15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629–0.811; maximum ΔC statistic from clinical score alone, 0.009–0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke, versus those in the lowest quartile (95%CI, 1.39–4.58; P=2.7×10−3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20–4.40; P=0.01). Conclusions Comprehensive AF genetic risk scores were associated with incident AF beyond clinical AF risk factors, with magnitudes of risk comparable to other clinical risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts to determine whether AF genetic risk may improve identification of subclinical AF or distinguish stroke mechanisms are warranted. PMID:27793994

Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical outcomes following transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial.

PubMed

Hengstenberg, Christian; Chandrasekhar, Jaya; Sartori, Samantha; Lefevre, Thierry; Mikhail, Ghada; Meneveau, Nicolas; Tron, Christophe; Jeger, Raban; Kupatt, Christian; Vogel, Birgit; Farhan, Serdar; Sorrentino, Sabato; Sharma, Madhav; Snyder, Clayton; Husser, Oliver; Boekstegers, Peter; Hambrecht, Rainer; Widder, Julian; Hildick-Smith, David; De Carlo, Marco; Wijngaard, Peter; Deliargyris, Efthymios; Bernstein, Debra; Baber, Usman; Mehran, Roxana; Anthopoulos, Prodromos; Dangas, George

2017-11-15

Prior studies have suggested that patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk for adverse cardiovascular events. Whether procedural bivalirudin compared with unfractionated heparin (UFH) has a beneficial effect on early outcomes in these patients is unknown. We examined for the effect of baseline or new-onset AF within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by AF status, on 30-day outcomes from the BRAVO 3 trial. The BRAVO-3 trial multicenter randomized trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined for 30-day Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic endpoints. Adjusted outcomes were analyzed using logistic regression methods. Of the study population, 41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR, whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE I compared with their counterparts without AF. Among AF and no-AF patients, there were no significant baseline differences between bivalirudin and UFH groups. At 30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs. 2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n = 38) was associated with significantly greater crude risk of 30-day stroke compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by anticoagulation type. Prior or new-onset AF is noted in more than one-third of patients undergoing transfemoral TAVR. Despite greater baseline comorbidities than non-AF patients, AF was not associated with significantly higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes were similar regardless of anticoagulant strategy in each group. © 2017 Wiley Periodicals, Inc.

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.

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

African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative.

PubMed

Perez, Marco V; Hoffmann, Thomas J; Tang, Hua; Thornton, Timothy; Stefanick, Marcia L; Larson, Joseph C; Kooperberg, Charles; Reiner, Alex P; Caan, Bette; Iribarren, Carlos; Risch, Neil

2013-09-01

Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans. © 2013.

Depression and Physical Inactivity as Confounding the Effect of Obesity on Atrial Fibrillation.

PubMed

Garimella, Roja S; Sears, Samuel F; Gehi, Anil K

2016-06-01

Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m(2)) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidence, type of atrial fibrillation and risk factors for stroke: a population-based cohort study

PubMed Central

Johansson, Cecilia; Dahlqvist, Erik; Andersson, Jonas; Jansson, Jan-Håkan; Johansson, Lars

2017-01-01

Purpose The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA2DS2-VASc score were obtained from medical records. Results The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged ≥80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA2DS2-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA2DS2-VASc score of 2 or more. PMID:28182159

Refinement of detecting atrial fibrillation in stroke patients: results from the TRACK-AF Study.

PubMed

Reinke, F; Bettin, M; Ross, L S; Kochhäuser, S; Kleffner, I; Ritter, M; Minnerup, J; Dechering, D; Eckardt, L; Dittrich, R

2018-04-01

Detection of occult atrial fibrillation (AF) is crucial for optimal secondary prevention in stroke patients. The AF detection rate was determined by implantable cardiac monitor (ICM) and compared to the prediction rate of the probability of incident AF by software based analysis of a continuously monitored electrocardiogram at follow-up (stroke risk analysis, SRA); an optimized AF detection algorithm is proposed by combining both tools. In a monocentric prospective study 105 out of 389 patients with cryptogenic stroke despite extensive diagnostic workup were investigated with two additional cardiac monitoring tools: (a) 20 months' monitoring by ICM and (b) SRA during hospitalization at the stroke unit. The detection rate of occult AF was 18% by ICM (n = 19) (range 6-575 days) and 62% (n = 65) had an increased risk for AF predicted by SRA. When comparing the predictive accuracy of SRA to ICM, the sensitivity was 95%, specificity 35%, positive predictive value 27% and negative predictive value 96%. In 18 patients with AF detected by ICM, SRA also showed a medium risk for AF. Only one patient with a very low risk predicted by SRA developed AF revealed by ICM after 417 days. A combination of SRA and ICM is a promising strategy to detect occult AF. SRA is reliable in predicting incident AF with a high negative predictive value. Thus, SRA may serve as a cost-effective pre-selection tool identifying patients at risk for AF who may benefit from further cardiac monitoring by ICM. © 2017 EAN.

A brief history of 'lone' atrial fibrillation: from 'a peculiar pulse irregularity' to a modern public health concern.

PubMed

Potpara, Tatjana S; Lip, Gregory Y H

2015-01-01

Ever since the original description of a 'peculiar pulse irregularity', atrial fibrillation (AF) has been studied extensively and has come a long journey from the recognition of its cardiac origins, to the modern concept of AF as a serious public health challenge with profound social and economic implications. This arrhythmia affects around 2% of adult population, and the most common underlying heart diseases accompanying AF in the modern era are hypertension, heart failure and coronary artery disease, as well as valvular heart diseases and numerous other cardiac as well as non-cardiac disorders which have been shown to predispose to AF. On occasions, AF occurs in young otherwise apparently healthy individuals (so called 'lone AF'). For a long time, 'lone' AF has been believed to bear a favourable prognosis as compared to AF with underlying structural heart disease, but increasing evidence suggests that 'lone' AF patients represent a rather heterogeneous cohort, with highly variable individual risk profiles due to the presence of various subclinical cardiovascular risk factors or genetically determined subtle alterations at the cellular or molecular level. For these reasons, the existence of truly 'lone' AF has recently been questioned. In this review article, we present a brief history of the recognition of the public health burden of AF. We discuss some of the misconceptions and breakthroughs on modern knowledge on AF, including the rise (and fall) of the 'lone' AF concept.

Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2007-08-01

Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community.

PubMed

Omboni, Stefano; Verberk, Willem J

2016-04-12

Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. 220 consecutive participants from an unselected sample of individuals in a small Italian community. Number of patients detected with AF and diagnosed risk factors for AF. In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats123

PubMed Central

Zhong, Wei; Li, Qiong; Sun, Qian; Zhang, Wenliang; Zhang, Jiayang; Sun, Xinguo; Yin, Xinmin; Zhang, Xiang; Zhou, Zhanxiang

2015-01-01

Background: Zinc deficiency has been well documented in alcoholic liver disease. Objective: This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-induced gut leakiness and endotoxemia. Methods: Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) Lieber-DeCarli liquid diet for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00–5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed with the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot analysis. Results: The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin concentrations of the AF rats were 136% greater than those of the PF rats, whereas the AF/Zn rats did not differ from the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group had reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group had upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with those of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group. Conclusions: The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats. PMID:26468492

Assessing intrinsic and specific vulnerability models ability to indicate groundwater vulnerability to groups of similar pesticides: A comparative study

USGS Publications Warehouse

Douglas, Steven; Dixon, Barnali; Griffin, Dale W.

2018-01-01

With continued population growth and increasing use of fresh groundwater resources, protection of this valuable resource is critical. A cost effective means to assess risk of groundwater contamination potential will provide a useful tool to protect these resources. Integrating geospatial methods offers a means to quantify the risk of contaminant potential in cost effective and spatially explicit ways. This research was designed to compare the ability of intrinsic (DRASTIC) and specific (Attenuation Factor; AF) vulnerability models to indicate groundwater vulnerability areas by comparing model results to the presence of pesticides from groundwater sample datasets. A logistic regression was used to assess the relationship between the environmental variables and the presence or absence of pesticides within regions of varying vulnerability. According to the DRASTIC model, more than 20% of the study area is very highly vulnerable. Approximately 30% is very highly vulnerable according to the AF model. When groundwater concentrations of individual pesticides were compared to model predictions, the results were mixed. Model predictability improved when concentrations of the group of similar pesticides were compared to model results. Compared to the DRASTIC model, the AF model more accurately predicts the distribution of the number of contaminated wells within each vulnerability class.

Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity.

PubMed

Linnemann, Amelia K; Krawetz, Stephen A

2009-05-01

DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14-18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment.

Effects of Heracleum persicum ethyl acetate extract on the growth, hyphal ultrastructure and aflatoxin biosynthesis in Aspergillus parasiticus.

PubMed

Razzaghi-Abyaneh, Mehdi; Saberi, Reza; Sharifan, Anosheh; Rezaee, Mohammad-Bagher; Seifili, Roghayeh; Hosseini, Seyed-Ibrahim; Shams-Ghahfarokhi, Masoomeh; Nikkhah, Mehdi; Saberi, Ismail; Amani, Akram

2013-11-01

The ethyl acetate extract of leaves, seeds and flowers of Heracleum persicum, a medicinal plant of Iran (family Apiaceae) inhibited growth and aflatoxin (AF) production of Aspergillus parasiticus. On the basis of total dry weight growth inhibition by the leaf extract ranged from 17.1 to 36.9 %, by the flower extract from 32.2 to 75.6 %, and by the seed extract from 27.5 to 74.9 %. Production of AFB1 and AFG1 was inhibited in a dose-dependent manner, with a reduction of 88.5-100 % at the highest concentration of 8,000 μg/ml tested. The flower extract decreased ergosterol content of hyphae most significantly. Electron microscopy further revealed structural defects in the treated A. parasiticus including disruption of cytoplasmic membranous compartments, detachment of plasma membrane from the cell wall, and disorganization of hyphal compartments. Collapsed hyphae without conidiation, shorter branches and undifferentiated hyphal tips were also evident. The results indicate that H. persicum extract exerts antifungal and anti-AF activities by disrupting plasma membrane integrity and permeability mainly through interference with ergosterol biosynthesis. These results show that H. persicum can serve as a potent and safe alternative for inhibiting toxigenic aspergilli growth and thus preventing AF contamination of foods and feeds.

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' compliance to CIG recommendations and their satisfaction and quality of life. Our evaluation has demonstrated the system's capability for supporting distributed decision-making and its use by patients and clinicians. The results show that compliance of GDM patients to the most important monitoring targets - blood glucose levels (performance of four measurements a day: 0.87±0.11; measurement according to the recommended frequency of every day or twice a week: 0.99±0.03), ketonuria (0.98±0.03), and blood pressure (0.82±0.24) - was high in most GDM patients, while compliance of AF patients to the most important targets was quite high, considering the required ECG measurements (0.65±0.28) and blood-pressure measurements (0.75±1.33). This outcome was viewed by the clinicians as a major potential benefit of the system, and the patients have demonstrated that they are capable of self-monitoring - something that they had not experienced before. In addition, the system caused the clinicians managing the AF patients to change their diagnosis and subsequent treatment for two of the ten AF patients, and caused the clinicians managing the GDM patients to start insulin therapy earlier in two of the 19 patients, based on system's recommendations. Based on the end-of-study questionnaires, the sense of safety that the system has provided to the patients was its greatest asset. Analysis of the patients' quality of life (QoL) questionnaires for the AF patients was inconclusive, because while most patients reported an improvement in their quality of life in the EuroQoL questionnaire, most AF patients reported a deterioration in the AFEQT questionnaire. Feasibility and some of the potential benefits of an evidence-based distributed patient-guidance system were demonstrated in both clinical domains. The potential application of MobiGuide to other medical domains is supported by its standards-based patient health record with multiple electronic medical record linking capabilities, generic data insertion methods, generic medical knowledge representation and application methods, and the ability to communicate with a wide range of sensors. Future larger scale evaluations can assess the impact of such a system on clinical outcomes. MobiGuide's feasibility was demonstrated by a working prototype for the AF and GDM domains, which is usable by patients and clinicians, achieving high compliance to self-measurement recommendations, while enhancing the satisfaction of patients and care providers. Copyright © 2017 Elsevier B.V. All rights reserved.

The efficacy of intraoperative atrial radiofrequency ablation for atrial fibrillation during concomitant cardiac surgery-the Surgical Atrial Fibrillation Suppression (SAFS) Study.

PubMed

Veasey, Rick A; Segal, Oliver R; Large, Janet K; Lewis, Michael E; Trivedi, Uday H; Cohen, Andrew S; Hyde, Jonathan A J; Sulke, A Neil

2011-10-01

Studies assessing radiofrequency ablation (RFA) for atrial fibrillation (AF) performed at the time of concomitant cardiac surgery have reported high success rates. The efficacy of this treatment has primarily been determined by a single electrocardiogram (ECG) or 24-h Holter monitor at follow-up. We sought to assess the true efficacy of this procedure using prolonged cardiac rhythm monitoring. One hundred patients with paroxysmal (n = 47) and persistent AF (n = 53) requiring cardiac surgery were enrolled. Patients were clinically reviewed 6 weeks post-operatively and were monitored with 7-day Holter with full disclosure, 6 months post-surgery. A cohort of 50 patients also underwent 7 day Holter monitoring preoperatively. AF recurrence was defined as >30 s of AF. At 6 months, 75% of patients were in sinus rhythm according to a single ECG. However, only 62% of patients were free from AF on 7-day Holter; all AF episodes in these patients were asymptomatic. The procedure resulted in a significant decrease in AF burden from 56.2% at baseline to 27.5% at 6 months follow-up, (p < 0.001). Predictors of AF recurrence were (1) pre-operative AF duration; (2) persistent compared with paroxysmal AF; (3) increasing left atrial diameter and (4) requirement for mitral valve surgery. Surgical RFA for the treatment of AF, during concomitant cardiac surgery, is a successful procedure and significantly reduces AF burden. However, 13% of patients have asymptomatic AF episodes only identified with continuous monitoring. This has important implications for post-operative anti-arrhythmic and anticoagulant management and for the definition of surgical AF ablation success.

Comparison of the origin and coupling interval between ectopy with and without atrial fibrillation initiation.

PubMed

Kanda, Takashi; Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2018-01-01

Differentiation of atrial fibrillation (AF) trigger ectopy from other ectopy is often difficult. The purpose of this study was to compare the origin and coupling intervals (CI) between AF-trigger and non-AF-trigger ectopy. This study consisted of 120 patients with AF who underwent an initial ablation. Isoproterenol was infused up to 20μg/min to provoke ectopy and AF. We measured the CI of all ectopy provoked by an isoproterenol infusion. The %CI was calculated as the CI of the ectopy/P-P interval of the preceding 2 beats. A total of 117 patients had at least one ectopy, and AF was induced in 56 (47%) patients. Of the 276 ectopies observed in this study, 211 (76%) originated from pulmonary veins and 77 (28%) were AF-trigger ectopy. AF-trigger ectopy more frequently originated from pulmonary veins (PVs) (74 vs. 3, p<0.001) and had a significantly shorter CI (201±70ms vs. 365±147ms, p<0.001) and lower %CI (29±11% vs. 55±14%, p<0.001) than that of non-AF-trigger ectopy. A receiver operating characteristics analysis revealed that a %CI of 40% was the best cut-off value for differentiating whether it was an AF-trigger or not. The identified trigger group, including patients with provoked AF-trigger ectopy or ectopy with a low %CI (<40%), had a significantly better AF recurrence-free survival rate than the other group (88% vs. 65%, p=0.004). AF-trigger ectopy predominantly originated from PVs and had a short CI. These findings may be useful for estimating whether ectopies are an AF-trigger or not. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

PubMed

Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

2017-06-01

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P <1×10 - 3 in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

Impact of Atrial Fibrillation on Healthcare Utilization in the Community: The Atherosclerosis Risk in Communities Study

PubMed Central

Bengtson, Lindsay G. S.; Lutsey, Pamela L.; Loehr, Laura R.; Kucharska‐Newton, Anna; Chen, Lin Y.; Chamberlain, Alanna M.; Wruck, Lisa M.; Duval, Sue; Stearns, Sally C.; Alonso, Alvaro

2014-01-01

Background Atrial fibrillation (AF) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF‐related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study. Methods and Results Participants with incident AF enrolled in fee‐for‐service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF, respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF, respectively. Most utilization among AF patients was attributable to non‐AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease–related reasons was 4.58 (95% CI: 3.41 to 6.16) for those with AF versus those without AF. The association between AF and healthcare utilization was similar among men and women and among white and black participants. Conclusions Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease–related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities. PMID:25359400

Increasing atrial fibrillation prevalence in acute ischemic stroke and TIA.

PubMed

Otite, Fadar Oliver; Khandelwal, Priyank; Chaturvedi, Seemant; Romano, Jose G; Sacco, Ralph L; Malik, Amer M

2016-11-08

To evaluate trends in atrial fibrillation (AF) prevalence in acute ischemic stroke (AIS) and TIA in the United States. We used the Nationwide Inpatient Sample to retrospectively compute weighted prevalence of AF in AIS (n = 4,355,140) and TIA (n = 1,816,459) patients admitted to US hospitals from 2004 to 2013. Multivariate-adjusted models were used to evaluate the association of AF with clinical factors, mortality, length of stay, and cost. From 2004 to 2013, AF prevalence increased by 22% in AIS (20%-24%) and by 38% in TIA (12%-17%). AF prevalence varied by age (AIS: 6% in 50-59 vs 37% in ≥80 years; TIA: 4% in 50-59 vs 24% in ≥80 years), sex (AIS: male 19% vs female 25%; TIA: male 15% vs female 14%), race (AIS: white 26% vs black 12%), and region (AIS: Northeast 25% vs South 20%). Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF in AIS. AF in AIS was a risk factor for in-hospital death (odds ratio 1.93, 95% confidence interval 1.89-1.98) but mortality in AIS with AF decreased from 11.6% to 8.3% (p < 0.001). Compared to no AF, AF was associated with increased cost of $2,310 and length of stay 1.1 days in AIS. AF prevalence in AIS and TIA has continued to increase. Disparity in AF prevalence in AIS and TIA exists by patient and hospital factors. AF is associated with increased mortality in AIS. Innovative AIS preventive strategies are needed in patients with AF, especially in the elderly. © 2016 American Academy of Neurology.

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.

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels

PubMed Central

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L.; Bhatnagar, Deepak; Cleveland, Thomas E.

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus. PMID:24734028

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels.

PubMed

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L; Bhatnagar, Deepak; Cleveland, Thomas E

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus.

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.

Benefit of Anticoagulation Therapy in Hyperthyroidism-Related Atrial Fibrillation.

PubMed

Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah

2015-08-01

Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.

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.

Atrial Fibrillation in Hypertrophic Cardiomyopathy: Prevalence, Clinical Correlations, and Mortality in a Large High‐Risk Population

PubMed Central

Siontis, Konstantinos C.; Geske, Jeffrey B.; Ong, Kevin; Nishimura, Rick A.; Ommen, Steve R.; Gersh, Bernard J.

2014-01-01

Background Atrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF, identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population. Methods and Results We identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF. The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM, 650 (18%) had AF. Patients with AF were older and more symptomatic (P<0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF (P<0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM, the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death. Conclusions In this large referral HCM population, approximately 1 in 5 patients had AF. AF was a strong predictor of mortality, even after adjustment for established risk factors. PMID:24965028

Morphologies of the atria and pulmonary veins in relation to lone atrial fibrillation progression: a dual-source computed tomography scan study.

PubMed

Liu, Xing-Peng; Xu, Xia; Tian, Ying; Tang, Ri-Bo; Yu, Rong-Hui; Long, De-Yong; Sang, Cai-Hua; Jiang, Chen-Xi; Ning, Man; Dong, Jian-Zeng; Ma, Chang-Sheng

2012-11-01

Atrial Remodeling and Lone Atrial Fibrillation. We sought to investigate the role of anatomic remodeling of the atria and pulmonary veins (PVs) in the progression of lone atrial fibrillation (AF) using dual-source computed tomography (DSCT). From 1,308 consecutive patients referred for an index ablation procedure for AF, we prospectively enrolled 29 consecutive patients with recently developed (<3 months) lone persistent AF (PsAF) and 23 consecutive patients with short-lasting (6-12 months) lone PsAF, all of whom had a history of paroxysmal AF (PAF). The control group consisted of 33 patients with lone PAF. On DSCT, the recently developed PsAF group showed more extensive atrial anatomic remodeling than the PAF group as shown by ∼40% higher spot biatrial volume, even though the mean duration of continuous AF was only 6 weeks. In contrast, the DSCT variables in the recently developed PsAF group and the short-lasting PsAF group were comparable, despite the fact that the mean duration of continuous AF in the latter group was 8 months. Series of cross-sectional areas of the ostial 1.5 cm of PV trunks were comparable in the PAF and PsAF groups in all but 3 ostial planes. A higher spot left atrial volume was the only independent factor associated with the progression of lone PAF to PsAF (OR: 1.06, 95% CI: 1.03-1.09, P<0.0001) on logistic regression. Prominent anatomic remodeling of the atria, rather than the PVs, underlies the mechanism of recent progression of lone paroxysmal AF to the persistent variety. © 2012 Wiley Periodicals, Inc.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

PubMed Central

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

2015-01-01

Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized 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 (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

The future of anticoagulation management in atrial fibrillation in Europe: An assessment of today's challenges with recommendations for the future.

PubMed

Lichten, Catherine A; Castle-Clarke, Sophie; Manville, Catriona; Horvath, Veronika; Robin, Enora; Krapels, Joachim; Parks, Sarah; Sim, Megan; van Zijverden, Olga; Chataway, Joanna

2015-11-30

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting approximately 1-2 per cent of the population worldwide. Those who suffer from AF have a five times higher risk of stroke. AF prevalence increases with age and it affects roughly 18 per cent of the population over 85. Consequently, as populations age, AF is becoming an increasingly significant public health issue. Over recent years there have been developments in treatment and management options, both for treating the arrhythmia directly, and assessing and reducing the risk of AF-related stroke, but there is a need to ensure that available knowledge is applied optimally to benefit patients so that opportunities to prevent AF-related stroke are not missed. The aims of this project were to assess the current landscape and explore the direction of future developments in AF management in Europe, with a focus on the use of anticoagulants in the prevention of AF-related stroke. Through rapid evidence assessment, key informant interviews, PESTLE analysis and the development and exploration of future scenarios, we have developed sets of shorter- and longer-term recommendations for improving AF-related patient outcomes. The short-term recommendations are: i) improve AF awareness among the public and policymakers; ii) support education about AF management for healthcare professionals and patients; and iii) maintain engagement in AF-related research across the health services.

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.

Novel pharmacological targets for the rhythm control management of atrial fibrillation.

PubMed

Burashnikov, Alexander; Antzelevitch, Charles

2011-12-01

Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Development of safe and effective pharmacological treatments for AF is one of the greatest unmet medical needs facing our society. In spite of significant progress in non-pharmacological AF treatments (largely due to the use of catheter ablation techniques), anti-arrhythmic agents (AADs) remain first line therapy for rhythm control management of AF for most AF patients. When considering efficacy, safety and tolerability, currently available AADs for rhythm control of AF are less than optimal. Ion channel inhibition remains the principal strategy for termination of AF and prevention of its recurrence. Practical clinical experience indicates that multi-ion channel blockers are generally more optimal for rhythm control of AF compared to ion channel-selective blockers. Recent studies suggest that atrial-selective sodium channel block can lead to safe and effective suppression of AF and that concurrent inhibition of potassium ion channels may potentiate this effect. An important limitation of the ion channel block approach for AF treatment is that non-electrical factors (largely structural remodeling) may importantly determine the generation of AF, so that "upstream therapy", aimed at preventing or reversing structural remodeling, may be required for effective rhythm control management. This review focuses on novel pharmacological targets for the rhythm control management of AF. Copyright © 2011 Elsevier Inc. All rights reserved.

Modulated exchange bias in NiFe/CoO/α-Fe2O3 trilayers and NiFe/CoO bilayers

NASA Astrophysics Data System (ADS)

Li, X.; Lin, K.-W.; Yeh, W.-C.; Desautels, R. D.; van Lierop, J.; Pong, Philip W. T.

2017-02-01

While the exchange bias in ferromagnetic/antiferromagnetic (FM/AF) bilayer and FM1/AF/FM2 trilayer configurations has been widely investigated, the role of an AF2 layer in FM/AF1/AF2 trilayer configurations is still not well understood. In this work, the magnetic properties of NiFe/CoO, NiFe/α-Fe2O3 bilayers, and NiFe/CoO/α-Fe2O3 trilayer were studied comparatively. The microstructure and chemical composition were characterized. Temperature dependent magnetometry reveals increased irreversibility temperature in NiFe/CoO/α-Fe2O3 trilayer compared with NiFe/CoO bilayer. The magnetic hysteresis loops show that the exchange bias (Hex) and coercivity (Hc) depend strongly on the anisotropy of AF layer (CoO, α-Fe2O3 and CoO/α-Fe2O3). Our work shows that the AF1/AF2 interfacial interactions can be used effectively for tuning the exchange bias in FM/AF1/AF2 trilayers.

Integrating Agile Combat Support within Title 10 Wargames

DTIC Science & Technology

2015-03-26

STAT C7 PCT TIME WAITING TO FLY D1 MANHOURS AVAILABLE D20 NMCM INDICATOR C8 ...Technology Graduate School of Engineering and Management (AFIT/ENS) 2950 Hobson Way, Building 640 WPAFB OH 45433-8865 8. PERFORMING ORGANIZATION...Branch Air Force Material Command Wright Patterson AFB, OH Email: omar.mendoza@us.af.mil 10. SPONSOR/MONITOR’S ACRONYM(S) AFMC/A4 11

Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein particles as a function of particle size in one workflow integrating asymmetric flow field-flow fractionation and liquid chromatography-tandem mass spectrometry

PubMed Central

Jones, Jeffery I.; Gardner, Michael S.; Schieltz, David M.; Parks, Bryan A.; Toth, Christopher A.; Rees, Jon C.; Andrews, Michael L.; Carter, Kayla; Lehtikoski, Antony K.; McWilliams, Lisa G.; Williamson, Yulanda M.; Bierbaum, Kevin P.; Pirkle, James L.; Barr, John R.

2018-01-01

Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples. PMID:29634782

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.

In permanent atrial fibrillation, PDE3 reduces force responses to 5‐HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias

PubMed Central

Schwarz, Simon; Ravens, Ursula; Knaut, Michael

2016-01-01

Abstract Background and Purpose 5‐HT increases force and L‐type Ca2 + current (ICa,L) and causes arrhythmias through 5‐HT4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5‐HT are blunted, arrhythmias abolished but ICa,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively. Experimental Approach Contractile force, arrhythmic contractions and ICa,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF. Key Results Maximum force responses to 5‐HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5‐HT in peAF and the inotropic potency of 5‐HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5‐HT were not decreased in peAF. Responses of ICa,L to 5‐HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5‐HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF. Conclusions and Implications PDE3, but not PDE4, reduced inotropic responses to 5‐HT in peAF, independently of lusitropy and ICa,L, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5‐HT to induce arrhythmias by inhibition of PDE3 plus PDE4. PMID:27238373

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 atrial fibrillation, PeAF= Persistent atrial fibrillation PUFA= Polyunsaturated fatty acid.

Photosynthesis Is Not Involved in the Mechanism of Action of Acifluorfen in Cucumber (Cucumis sativus L.)

PubMed Central

Duke, Stephen O.; Kenyon, William H.

1986-01-01

The possible role of photosynthesis in the mechanism of action of the herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate; AF) was examined. The sensitivity to AF of cotyledons of cucumber (Cucumis sativus L.) which had been grown under far red light (FR) and white light were compared. FR grown tissues which were photosynthetically imcompetent were hypersensitive to AF under white light and had approximately the same relative response to AF under blue and red light as green, white-light-grown tissues. Ultrastructural damage was apparent in FR-grown, AF-treated tissues within an hour after exposure to white light, with cytoplasmic and plastidic disorganization occurring simultaneously. In cucumber cotyledon tissue which had been greening for various time periods, there was no correlation between photosynthetic capacity and herbicidal efficacy of AF. PSII inhibitors (atrazine and DCMU) and the photophosphorylation inhibitor, tentoxin, had no effect on AF activity. Atrazine did not reduce AF activity at any concentration or light intensity tested, indicating that there is no second, photosynthetic-dependent mechanism of action operating at low AF concentrations or low fluence rates. Carbon dioxide-dependent O2 evolution of intact chloroplasts of spinach (Spinacia oleracea L.) had an AF I50 of 125 micromolar compared to 1000 micromolar for cucumber, whereas AF was much more herbicidally active in tissues of cucumber than of spinach. Differences in activity could not be accounted for by differences in uptake of AF. Our results indicate that there is no photosynthetic involvement in the mechanism of action of AF in cucumber. Images Fig. 2 PMID:16664919

Prospective study of atrial fibrillation termination during ablation guided by automated detection of fractionated electrograms.

PubMed

Porter, Michael; Spear, William; Akar, Joseph G; Helms, Ray; Brysiewicz, Neil; Santucci, Peter; Wilber, David J

2008-06-01

Complex fractionated atrial electrograms (CFAE) may identify critical sites for perpetuation of atrial fibrillation (AF) and provide useful targets for ablation. Current assessment of CFAE is subjective; automated detection algorithms may improve reproducibility, but their utility in guiding ablation has not been tested. In 67 patients presenting for initial AF ablation (42 paroxysmal, 25 persistent), LA and CS mapping were performed during induced or spontaneous AF. CFAE were identified by an online automated computer algorithm and displayed on electroanatomical maps. A mean of 28 +/- 18 sites/patient were identified (20 +/- 13% of mapped sites), and were more frequent during persistent AF. CFAE occurred most commonly within the CS, on the atrial septum, and around the pulmonary veins. Ablation initially targeting CFAE terminated AF in 88% of paroxysmal AF, but only 20% of persistent AF (P < 0.001). Subsequently, additional ablation was performed in all patients (PV isolation for paroxysmal AF, PV isolation + mitral and roof lines for persistent AF). Minimum follow-up was 1 year. One-year freedom from recurrent atrial arrhythmias without antiarrhythmic drug therapy after a single procedure was 90% for paroxysmal AF, and 68% for persistent AF. Ablation guided by automated detection of CFAE proved feasible, and was associated with a high AF termination rate in paroxysmal, but not persistent AF. As an adjunct to conventional techniques, it was associated with excellent long-term single procedure outcomes in both groups. Criteria for identifying optimal CFAE sites for ablation, and selection of patients most likely to benefit, require additional study.

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.

Successful Repeat Catheter Ablation of Recurrent Longstanding Persistent Atrial Fibrillation With Rotor Elimination as the Procedural Endpoint: A Case Series.

PubMed

Sommer, Philipp; Kircher, Simon; Rolf, Sascha; John, Silke; Arya, Arash; Dinov, Borislav; Richter, Sergio; Bollmann, Andreas; Hindricks, Gerhard

2016-03-01

There remains a lack of consensus regarding the ideal ablation strategy for atrial fibrillation (AF), particularly in patients with persistent or longstanding persistent AF. Given increasing evidence from clinical imaging studies that rotors sustain AF, rotor elimination may be a desirable procedural endpoint. However, there is no description to date of the clinical outcomes using rotor elimination during ablation as the procedural endpoint. Moreover, a series of studies question whether procedural AF termination is a desirable endpoint for ablation after many forms of AF ablation. We report a single-center experience of rotor elimination during AF ablation using Focal Impulse and Rotor Mapping (FIRM), describing 20 consecutive patients with case descriptions of 3 patients with recurrent longstanding persistent AF after prior ablation. In all cases, endocardial mapping using a 64-electrode basket catheter was performed to identify rotors, which were eliminated using radiofrequency catheter ablation. After it was verified that all identified rotors were eliminated, standard ablation consisting of PV isolation was performed. Notably, persistent AF terminated in only 1/20 (5%) patients. However, after a follow-up of 6 months, single-procedure freedom from AF was 80% (16/20 patients) with only 1 patient on antiarrhythmic drugs. All three patients in the highlighted series are AF free despite the lack of acute procedural AF termination. Patients with persistent AF including those with unsuccessful prior ablation can be treated successfully by rotor targeted ablation, using the elimination of all rotors rather than acute AF termination as the procedural endpoint. © 2015 Wiley Periodicals, Inc.

Continuous ECG monitoring for tracking down atrial fibrillation after stroke: Holter or automated analysis strategy?

PubMed

Suissa, Laurent; Lachaud, Sylvain; Mahagne, Marie-Hélène

2014-01-01

Tracking down atrial fibrillation (AF) in the stroke unit is a relevant challenge for the prevention of recurrent AF-related stroke. The optimal terms of use of continuous ECG monitoring (CEM) are unknown. We compared 24-hour routine Holter ECG with two different CEM analysis strategies for AF detection. We prospectively enrolled consecutive ischemic stroke patients. All AF-naïve patients received CEM during hospitalization. Two methods for reading CEM data were compared: manual analysis using the Holter function (hCEM) and semiautomated analysis using software (aCEM). The McNemar test was used to compare AF detection rates. Of the 362 patients included, 58 (16.0%) were non-AF-naïve patients and 304 were AF-naïve patients. AF-Naïve patients underwent CEM with a median duration of 5.3 days (3.4-9.7). We detected 22 new AF cases (7.2%) with first-24-hour hCEM, 31 (10.2%) with aCEM, and 42 (13.8%) with hCEM. hCEM and aCEM both significantly increased the AF detection rate compared to first-24-hour hCEM. hCEM detected more new AF cases than aCEM (+3.6%, p = 0.003). In stroke patients, early and prolonged aCEM and hCEM both increase the AF detection rate compared to first-24-hour hCEM. hCEM gives the best AF detection rate. We suggest that in aCEM, detection based only on the ventricular rhythm analysis explains its lower specificity and sensitivity. © 2014 S. Karger AG, Basel.

A structured reading algorithm improves telemetric detection of atrial fibrillation after acute ischemic stroke.

PubMed

Kallmünzer, Bernd; Breuer, Lorenz; Hering, Christiane; Raaz-Schrauder, Dorette; Kollmar, Rainer; Huttner, Hagen B; Schwab, Stefan; Köhrmann, Martin

2012-04-01

Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. Median effective telemetry monitoring time was 75.5 hours (interquartile range 64-86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

A systematic review of the health benefits of exercise rehabilitation in persons living with atrial fibrillation.

PubMed

Giacomantonio, Nicholas B; Bredin, Shannon S D; Foulds, Heather J A; Warburton, Darren E R

2013-04-01

This systematic review sought to evaluate critically the health benefits of physical activity among persons with atrial fibrillation (AF). AF is increasing in Western society. While health benefits of physical activity are well established, benefits of physical activity among individuals with AF are not clearly identified. Literature was retrieved systematically through searching electronic databases (MEDLINE, EMBASE, Cochrane), cross-referencing, and drawing on the authors' knowledge. Identified original research articles evaluated health benefits of physical activity among persons with AF or effects of physical activity on AF incidence. From 1056 individual citations, 36 eligible articles were identified. Moderate-intensity physical activity was found to improve exercise capacity, quality of life, and the ability to carry out activities of daily living among persons with AF (n = 6). Increased incidence of AF was not associated with physical activity among the general population (n = 2), although long-term vigorous endurance exercise may be associated with increased incidence of AF (n = 7), and greater risks may be associated with high-intensity physical activity among those with AF (n = 2). Moderate-intensity physical activity among individuals with AF does not adversely alter training outcomes, functional capacity, morbidity, or mortality compared with those in sinus rhythm (n = 12). Physical activity may improve management and treatment of AF (n = 6) and, among at-risk populations, may reduce incidence of AF (n = 3). In conclusion, moderate-intensity physical activity should be encouraged among persons with or at risk of AF. Further research is needed. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

PubMed Central

Pellman, Jason; Sheikh, Farah

2017-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca2+ current, various K+ currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. PMID:25880508

Immune Regulatory Properties of CD117pos Amniotic Fluid Stem Cells Vary According to Gestational Age

PubMed Central

Di Trapani, Mariano; Bassi, Giulio; Fontana, Emanuela; Giacomello, Luca; Pozzobon, Michela; Guillot, Pascale V.; De Coppi, Paolo

2015-01-01

Amniotic Fluid Stem (AFS) cells are broadly multipotent fetal stem cells derived from the positive selection and ex vivo expansion of amniotic fluid CD117/c-kitpos cells. Considering the differentiation potential in vitro toward cell lineages belonging to the three germ layers, AFS cells have raised great interest as a new therapeutic tool, but their immune properties still need to be assessed. We analyzed the in vitro immunological properties of AFS cells from different gestational age in coculture with T, B, and natural killer (NK) cells. Nonactivated (resting) first trimester-AFS cells showed lower expression of HLA class-I molecules and NK-activating ligands than second and third trimester-AFS cells, whose features were associated with lower sensitivity to NK cell-mediated lysis. Nevertheless, inflammatory priming with interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) enhanced resistance of all AFS cell types to NK cytotoxicity. AFS cells modulated lymphocyte proliferation in a different manner according to gestational age: first trimester-AFS cells significantly inhibited T and NK cell proliferation, while second and third trimester-AFS cells were less efficient. In addition, only inflammatory-primed second trimester-AFS cells could suppress B cell proliferation, which was not affected by the first and third trimester-AFS cells. Indolamine 2,3 dioxygenase pathway was significantly involved only in T cell suppression mediated by second and third trimester-AFS cells. Overall, this study shows a number of significant quantitative differences among AFS cells of different gestational age that have to be considered in view of their clinical application. PMID:25072397

Lone atrial fibrillation: where are we now?

PubMed

Potpara, Tatjana S; Lip, Gregory Y

2011-10-01

There is a growing pandemic of atrial fibrillation (AF), affecting nearly 2% of the general adult population. Atrial fibrillation is commonly associated with structural heart disease, and AF itself causes a sequence of complex processes of electrical, contractile, and structural remodeling of the atrial myocardium, which facilitate further AF progression. Nonetheless, AF may also affect individuals aged ≤ 65 years who have no evidence of associated cardiopulmonary or other disease, including hypertension; this is otherwise referred to as "lone" AF and is considered to have a generally favorable prognosis. The true prevalence of lone AF is unknown. Growing insights into the diversity of numerous mechanisms involved in the pathogenesis of AF, including acute atrial stretch, structural and electrophysiological alterations, systemic inflammation, oxidative stress, autonomic imbalance, genetic predisposition, and many others, and increasing recognition of novel risk factors for AF, including obesity, metabolic syndrome, subclinical atherosclerosis, sleep apnea, alcohol consumption, and endurance sports, suggest that apparently lone AF might not be so "lone" in many patients, which could have important prognostic and therapeutic implications. In this article, we summarize the current knowledge of epidemiology, etiopathogenesis, and pathophysiology of so-called lone AF and discuss the issues of long-term prognosis and management of patients who have an apparently lone AF.

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

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

Rhythm-based heartbeat duration normalization for atrial fibrillation detection.

PubMed

Islam, Md Saiful; Ammour, Nassim; Alajlan, Naif; Aboalsamh, Hatim

2016-05-01

Screening of atrial fibrillation (AF) for high-risk patients including all patients aged 65 years and older is important for prevention of risk of stroke. Different technologies such as modified blood pressure monitor, single lead ECG-based finger-probe, and smart phone using plethysmogram signal have been emerging for this purpose. All these technologies use irregularity of heartbeat duration as a feature for AF detection. We have investigated a normalization method of heartbeat duration for improved AF detection. AF is an arrhythmia in which heartbeat duration generally becomes irregularly irregular. From a window of heartbeat duration, we estimate the possible rhythm of the majority of heartbeats and normalize duration of all heartbeats in the window based on the rhythm so that we can measure the irregularity of heartbeats for both AF and non-AF rhythms in the same scale. Irregularity is measured by the entropy of distribution of the normalized duration. Then we classify a window of heartbeats as AF or non-AF by thresholding the measured irregularity. The effect of this normalization is evaluated by comparing AF detection performances using duration with the normalization, without normalization, and with other existing normalizations. Sensitivity and specificity of AF detection using normalized heartbeat duration were tested on two landmark databases available online and compared with results of other methods (with/without normalization) by receiver operating characteristic (ROC) curves. ROC analysis showed that the normalization was able to improve the performance of AF detection and it was consistent for a wide range of sensitivity and specificity for use of different thresholds. Detection accuracy was also computed for equal rates of sensitivity and specificity for different methods. Using normalized heartbeat duration, we obtained 96.38% accuracy which is more than 4% improvement compared to AF detection without normalization. The proposed normalization method was found useful for improving performance and robustness of AF detection. Incorporation of this method in a screening device could be crucial to reduce the risk of AF-related stroke. In general, the incorporation of the rhythm-based normalization in an AF detection method seems important for developing a robust AF screening device. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advancing the literature on designing audit and feedback interventions: identifying theory-informed hypotheses.

PubMed

Colquhoun, Heather L; Carroll, Kelly; Eva, Kevin W; Grimshaw, Jeremy M; Ivers, Noah; Michie, Susan; Sales, Anne; Brehaut, Jamie C

2017-09-29

Audit and feedback (A&F) is a common strategy for helping health providers to implement evidence into practice. Despite being extensively studied, health care A&F interventions remain variably effective, with overall effect sizes that have not improved since 2003. Contributing to this stagnation is the fact that most health care A&F interventions have largely been designed without being informed by theoretical understanding from the behavioral and social sciences. To determine if the trend can be improved, the objective of this study was to develop a list of testable, theory-informed hypotheses about how to design more effective A&F interventions. Using purposive sampling, semi-structured 60-90-min telephone interviews were conducted with experts in theories related to A&F from a range of fields (e.g., cognitive, health and organizational psychology, medical decision-making, economics). Guided by detailed descriptions of A&F interventions from the health care literature, interviewees described how they would approach the problem of designing improved A&F interventions. Specific, theory-informed hypotheses about the conditions for effective design and delivery of A&F interventions were elicited from the interviews. The resulting hypotheses were assigned by three coders working independently into themes, and categories of themes, in an iterative process. We conducted 28 interviews and identified 313 theory-informed hypotheses, which were placed into 30 themes. The 30 themes included hypotheses related to the following five categories: A&F recipient (seven themes), content of the A&F (ten themes), process of delivery of the A&F (six themes), behavior that was the focus of the A&F (three themes), and other (four themes). We have identified a set of testable, theory-informed hypotheses from a broad range of behavioral and social science that suggest conditions for more effective A&F interventions. This work demonstrates the breadth of perspectives about A&F from non-healthcare-specific disciplines in a way that yields testable hypotheses for healthcare A&F interventions. These results will serve as the foundation for further work seeking to set research priorities among the A&F research community.

Rabbit notochordal cells modulate the expression of inflammatory mediators by human annulus fibrosus cells cocultured with activated macrophage-like THP-1 cells.

PubMed

Kim, Joo Han; Moon, Hong Joo; Lee, Jin Hoon; Kim, Jong Hyun; Kwon, Taek Hyun; Park, Youn Kwan

2012-10-15

We evaluated the influence of rabbit notochordal cells on the expression of inflammatory mediators by human annulus fibrosus (AF) cells cocultured with macrophage-like cells. To identify the protective effect of rabbit notochordal cells on AF during in vitro inflammation. Discogenic pain, which is an important cause of intractable lower back pain, is associated with macrophage-mediated inflammation in the AF. Although rabbit notochordal cells prevent intervertebral disc degeneration, their effects on human AF inflammation remain unknown. Human AF pellets were cocultured for 48 hours with notochordal cell clusters from adult New Zealand White rabbits and phorbol myristate acetate (PMA)-stimulated human macrophage-like THP-1 cells. Conditioned media (CM) from the cocultures were assayed by enzyme-linked immunosorbent assay. The expression of inflammatory mediators in the AF pellets was evaluated by real-time reverse-transcription polymerase chain reaction. The levels of mRNA for interleukin (IL)-6, IL-8, and inducible nitric oxide synthase (iNOS) in the AF pellets cocultured with notochordal cells and macrophages (hAF[rNC-M]) were significantly lower than those in the AF pellets cultured with macrophages alone (hAF[M]) (P < 0.05). The levels of IL-6 and IL-8 proteins in the CM of hAF(rNC-M) were significantly lower than those in the CM of hAF(M) (P < 0.05). Coculturing with notochordal cells significantly decreased the levels of mRNA for IL-6, IL-8, and iNOS in the macrophage-exposed AF pellets (P < 0.05). After 1 ng/mL IL-1β stimulation, the levels of IL-6 and IL-8 mRNA and the level of IL-8 protein production were significantly decreased in the AF pellets with notochordal cells compared with naïve AF pellets (P < 0.05). In an in vitro coculture system, rabbit notochordal cells reduced the levels of main inflammatory mediators and gene expression in the human AF during inflammation. Therefore, rabbit notochordal cells may constitute an important protective tool against symptomatic disc development.

The impact of the CartoSound® image directly acquired from the left atrium for integration in atrial fibrillation ablation.

PubMed

Kaseno, Kenichi; Hisazaki, Kaori; Nakamura, Kohki; Ikeda, Etsuko; Hasegawa, Kanae; Aoyama, Daisetsu; Shiomi, Yuichiro; Ikeda, Hiroyuki; Morishita, Tetsuji; Ishida, Kentaro; Amaya, Naoki; Uzui, Hiroyasu; Tada, Hiroshi

2018-04-14

Intracardiac echocardiographic (ICE) imaging might be useful for integrating three-dimensional computed tomographic (CT) images for left atrial (LA) catheter navigation during atrial fibrillation (AF) ablation. However, the optimal CT image integration method using ICE has not been established. This study included 52 AF patients who underwent successful circumferential pulmonary vein isolation (CPVI). In all patients, CT image integration was performed after the CPVI with the following two methods: (1) using ICE images of the LA derived from the right atrium and right ventricular outflow tract (RA-merge) and (2) using ICE images of the LA directly derived from the LA added to the image for the RA-merge (LA-merge). The accuracy of these two methods was assessed by the distances between the integrated CT image and ICE image (ICE-to-CT distance), and between the CT image and actual ablated sites for the CPVI (CT-to-ABL distance). The mean ICE-to-CT distance was comparable between the two methods (RA-merge = 1.6 ± 0.5 mm, LA-merge = 1.7 ± 0.4 mm; p = 0.33). However, the mean CT-to-ABL distance was shorter for the LA-merge (2.1 ± 0.6 mm) than RA-merge (2.5 ± 0.8 mm; p < 0.01). The LA, especially the left-sided PVs and LA roof, was more sharply delineated by direct LA imaging, and whereas the greatest CT-to-ABL distance was observed at the roof portion of the left superior PV (3.7 ± 2.8 mm) after the RA-merge, it improved to 2.6 ± 1.9 mm after the LA-merge (p < 0.01). Additional ICE images of the LA directly acquired from the LA might lead to a greater accuracy of the CT image integration for the CVPI.

Chemistry of 1,1,2,2,9,9,10,10-octafluoro-[2,2]-paracyclophane: Its synthesis and reactions

NASA Astrophysics Data System (ADS)

Duan, Jian-Xin

This dissertation describes the first example of the synthesis of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane (AF4) under non-high-dilution conditions. Under very mild reaction conditions, bis-p-(chlorodifluoromethyl)benzene (TFPX dichloride) and its derivatives reacted with Zn dust in N,N-dimethyl acetamide (DMA) (Zinc method) affording the corresponding AF4 and its derivatives in moderate to good yields. Purification of products was also studied and an efficient purification process was developed. A new and very cheap method for preparation of TFPX dichloride is also disclosed. Using the very cheap fluorinating reagent, anhydrous hydrogen fluoride (AHF), 1,4-bis(trichloromethyl)benezene or its derivatives were converted to TFPX and its derivatives in high yields (F/Cl exchange reaction). With the success of the Zinc method and F/Cl exchange reaction, highly pure AF4 thus can be provided to the semiconductor industry and academy research scientists in large quantity and at a very low price. Starting from AF4, numerous AF4 derivatives were synthesized using convenient reaction conditions. Reaction of AF4 with fuming nitric acid at room temperature gave mono-nitroAF4 in almost quantitative yield. Reduction of the mono-nitroAF4 with iron powder in the presence of HCl in alcoholic solvent gave the aminoAF4 in 90% yield. Via the diazonium salt intermediate, iodoAF4 was also obtained in good yield. Under similar reaction conditions, disubstituted AF4 derivatives were also prepared in good yields. Heating a mixture of AF4, trifluoroacetyl peroxide and dichloromethane gave the trifluoromethylated dimeric AF4 as a mixture of diastereomers. When these products were heated to 170--180°C in the presence of I 2, 4-trifluoromethyl-AF4 was obtained in almost 87% yield. X-ray structural analysis showed that the C-C bond connecting the two cyclophane moieties to be longer than the normal C-C bond. Kinetic studies, conducted in the presence of excess amount of hydrogen donor, showed this bond to be quite weak. Oxidation of AF4 with HIO3 in the presence of catalytic amount of H2SO4 in trifluoroacetic acid gave AF4 quinone in one step. AF4 quinone can be easily reduced to the hydroquinone by Na 2S2O4 aqueous solution.

Porous silicon photoluminescence biosensor for rapid and sensitive detection of toxins

NASA Astrophysics Data System (ADS)

Melnyk, Yulia; Pavlova, Karyna; Myndrul, Valerii; Viter, Roman; Smyntyna, Valentyn; Iatsunskyi, Igor

2017-08-01

A rapid and low cost photoluminescence (PL) immunosensor for the determination of low concentrations of Ochratoxin A(OTA) and Aflatoxine B1 (AfB1) has been developed. This biosensor was based on porous silicon (PSi) fabricated by metal-assisted chemical etching (MACE) and modified by antibodies against OTA/AfB1 (anti-OTA/anti-AfB1). Biofunctionalization method of the PSi surface by anti-OTA/ anti-AfB1 was developed. The changes of the PL intensity after interaction of the immobilized anti-OTA/anti-AfB1with OTA/AfB1 antigens were used as biosensor signal, allowing sensitive and selective detection of OTA/AfB1 antigens in BSA solution. The sensitivity of the reported optical biosensor towards OTA/AfB1 antigens is in the range from 10-3 to 102 ng/ml.

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

Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia.

PubMed

Xue, Kanmin; Oldani, Marta; Jolly, Jasleen K; Edwards, Thomas L; Groppe, Markus; Downes, Susan M; MacLaren, Robert E

2016-07-01

To evaluate the relationships between RPE, photoreceptor, and choroidal degeneration in choroideremia. Enhanced-depth imaging optical coherence tomography (EDI-OCT), scanning laser ophthalmoscopy (SLO), and autofluorescence (AF) were performed on 39 patients (78 eyes) with choroideremia. The edges of surviving outer retina on OCT and residual AF were aligned. The distribution of outer retinal tubulations was mapped over a range of ages (16-71 years), and comparison made between pre- and postsubretinal gene therapy. Subfoveal choroidal thickness (SFCT) was compared between 23 choroideremia patients (42 eyes) and 20 age- and refraction-matched male controls (40 eyes). The edges of RPE AF aligned with a reduction in outer nuclear layer thickness (Spearman's rho = 0.9992). Correlation was also found between the quality of AF and integrity of ellipsoid zone within islands of surviving retina. Tubulations existed in 71 of 78 (91%) eyes with choroideremia and remained stable following gene therapy. Subfoveal choroidal thickness was reduced at baseline in choroideremia (179.7 ± 17.2 μm) compared with controls (302.0 ± 4.8 μm; P < 0.0001), but did not undergo significant thinning until end-stage retinal degeneration (43.1 ± 6.5 μm). The data suggest that RPE loss is the primary cause of photoreceptor degeneration in choroideremia. The choroid is thinner than controls from early stages, in keeping with a mild developmental defect. Photoreceptors appear to lose outer segments following loss of underlying RPE and form tubulations at the edges of degeneration. The preservation of tubulations over time and after subretinal injection would be consistent with these structures maintaining attachment to the inner retina and hence being potentially light responsive (ClinicalTrials.gov, NCT01461213).

Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia

PubMed Central

Xue, Kanmin; Oldani, Marta; Jolly, Jasleen K.; Edwards, Thomas L.; Groppe, Markus; Downes, Susan M.; MacLaren, Robert E.

2016-01-01

Purpose To evaluate the relationships between RPE, photoreceptor, and choroidal degeneration in choroideremia. Methods Enhanced-depth imaging optical coherence tomography (EDI-OCT), scanning laser ophthalmoscopy (SLO), and autofluorescence (AF) were performed on 39 patients (78 eyes) with choroideremia. The edges of surviving outer retina on OCT and residual AF were aligned. The distribution of outer retinal tubulations was mapped over a range of ages (16–71 years), and comparison made between pre- and postsubretinal gene therapy. Subfoveal choroidal thickness (SFCT) was compared between 23 choroideremia patients (42 eyes) and 20 age- and refraction-matched male controls (40 eyes). Results The edges of RPE AF aligned with a reduction in outer nuclear layer thickness (Spearman's rho = 0.9992). Correlation was also found between the quality of AF and integrity of ellipsoid zone within islands of surviving retina. Tubulations existed in 71 of 78 (91%) eyes with choroideremia and remained stable following gene therapy. Subfoveal choroidal thickness was reduced at baseline in choroideremia (179.7 ± 17.2 μm) compared with controls (302.0 ± 4.8 μm; P < 0.0001), but did not undergo significant thinning until end-stage retinal degeneration (43.1 ± 6.5 μm). Conclusions The data suggest that RPE loss is the primary cause of photoreceptor degeneration in choroideremia. The choroid is thinner than controls from early stages, in keeping with a mild developmental defect. Photoreceptors appear to lose outer segments following loss of underlying RPE and form tubulations at the edges of degeneration. The preservation of tubulations over time and after subretinal injection would be consistent with these structures maintaining attachment to the inner retina and hence being potentially light responsive (ClinicalTrials.gov, NCT01461213). PMID:27403996

Magnetotransport of multiple-band nearly antiferromagnetic metals due to hot-spot scattering

DOE PAGES

Koshelev, A. E.

2016-09-30

Multiple-band electronic structure and proximity to antiferromagnetic (AF) instability are the key properties of iron-based superconductors. In this paper, we explore the influence of scattering by the AF spin fluctuations on transport of multiple-band metals above the magnetic transition. A salient feature of scattering on the AF fluctuations is that it is strongly enhanced at the Fermi surface locations where the nesting is perfect (“hot spots” or “hot lines”). We review derivation of the collision integral for the Boltzmann equation due to AF-fluctuations scattering. In the paramagnetic state, the enhanced scattering rate near the hot lines leads to anomalous behaviormore » of electronic transport in magnetic field. We explore this behavior by analytically solving the Boltzmann transport equation with approximate transition rates. This approach accounts for return scattering events and is more accurate than the relaxation-time approximation. The magnetic-field dependences are characterized by two very different field scales: the lower scale is set by the hot-spot width and the higher scale is set by the total scattering amplitude. A conventional magnetotransport behavior is limited to magnetic fields below the lower scale. In the wide range in-between these two scales, the longitudinal conductivity has linear dependence on the magnetic field and the Hall conductivity has quadratic dependence. The linear dependence of the diagonal component reflects growth of the Fermi-surface area affected by the hot spots proportional to the magnetic field. Finally, we discuss applicability of this theoretical framework for describing of anomalous magnetotransport properties in different iron pnictides and chalcogenides in the paramagnetic state.« less

Personalized and automated remote monitoring of atrial fibrillation.

PubMed

Rosier, Arnaud; Mabo, Philippe; Temal, Lynda; Van Hille, Pascal; Dameron, Olivier; Deléger, Louise; Grouin, Cyril; Zweigenbaum, Pierre; Jacques, Julie; Chazard, Emmanuel; Laporte, Laure; Henry, Christine; Burgun, Anita

2016-03-01

Remote monitoring of cardiac implantable electronic devices is a growing standard; yet, remote follow-up and management of alerts represents a time-consuming task for physicians or trained staff. This study evaluates an automatic mechanism based on artificial intelligence tools to filter atrial fibrillation (AF) alerts based on their medical significance. We evaluated this method on alerts for AF episodes that occurred in 60 pacemaker recipients. AKENATON prototype workflow includes two steps: natural language-processing algorithms abstract the patient health record to a digital version, then a knowledge-based algorithm based on an applied formal ontology allows to calculate the CHA2DS2-VASc score and evaluate the anticoagulation status of the patient. Each alert is then automatically classified by importance from low to critical, by mimicking medical reasoning. Final classification was compared with human expert analysis by two physicians. A total of 1783 alerts about AF episode >5 min in 60 patients were processed. A 1749 of 1783 alerts (98%) were adequately classified and there were no underestimation of alert importance in the remaining 34 misclassified alerts. This work demonstrates the ability of a pilot system to classify alerts and improves personalized remote monitoring of patients. In particular, our method allows integration of patient medical history with device alert notifications, which is useful both from medical and resource-management perspectives. The system was able to automatically classify the importance of 1783 AF alerts in 60 patients, which resulted in an 84% reduction in notification workload, while preserving patient safety. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The Science of Cost-Effective Materials Design - A Study in the Development of a High Strength, Impact Resistant Steel

NASA Astrophysics Data System (ADS)

Abrahams, Rachel

2017-06-01

Intermediate alloy steels are widely used in applications where both high strength and toughness are required for extreme/dynamic loading environments. Steels containing greater than 10% Ni-Co-Mo are amongst the highest strength martensitic steels, due to their high levels of solution strengthening, and preservation of toughness through nano-scaled secondary hardening, semi-coherent hcp-M2 C carbides. While these steels have high yield strengths (σy 0.2 % >1200 MPa) with high impact toughness values (CVN@-40 >30J), they are often cost-prohibitive due to the material and processing cost of nickel and cobalt. Early stage-I steels such as ES-1 (Eglin Steel) were developed in response to the high cost of nickel-cobalt steels and performed well in extreme shock environments due to the presence of analogous nano-scaled hcp-Fe2.4 C epsilon carbides. Unfortunately, the persistence of W-bearing carbides limited the use of ES-1 to relatively thin sections. In this study, we discuss the background and accelerated development cycle of AF96, an alternative Cr-Mo-Ni-Si stage-I temper steel using low-cost heuristic and Integrated Computational Materials Engineering (ICME)-assisted methods. The microstructure of AF96 was tailored to mimic that of ES-1, while reducing stability of detrimental phases and improving ease of processing in industrial environments. AF96 is amenable to casting and forging, deeply hardenable, and scalable to 100,000 kg melt quantities. When produced at the industrial scale, it was found that AF96 exhibits near-statistically identical mechanical properties to ES-1 at 50% of the cost.

Simultaneous Alcoholic and Malolactic Fermentations by Saccharomyces cerevisiae and Oenococcus oeni Cells Co-immobilized in Alginate Beads

PubMed Central

Bleve, Gianluca; Tufariello, Maria; Vetrano, Cosimo; Mita, Giovanni; Grieco, Francesco

2016-01-01

Malolactic fermentation (MLF) usually takes place after the end of alcoholic fermentation (AF). However, the inoculation of lactic acid bacteria together with yeast starter cultures is a promising system to enhance the quality and safety of wine. In recent years, the use of immobilized cell systems has been investigated, with interesting results, for the production of different fermented foods and beverages. In this study we have carried out the simultaneous immobilization of Saccharomyces cerevisiae and Oenococcus oeni in alginate beads and used them in microvinifications tests to produce Negroamaro wine. The process was monitored by chemical and sensorial analyses and dominance of starters and cell leaking from beads were also checked. Co-immobilization of S. cerevisiae and O. oeni allowed to perform an efficient fermentation process, producing low volatile acidity levels and ethanol and glycerol concentrations comparable with those obtained by cell sequential inoculum and co-inoculum of yeast and bacteria cells in free form. More importantly, co-immobilization strategy produced a significant decrease of the time requested to complete AF and MLF. The immobilized cells could be efficiently reused for the wine fermentation at least three times without any apparent loss of cell metabolic activities. This integrated biocatalytic system is able to perform simultaneously AF and MLF, producing wines similar in organoleptic traits in comparison with wines fermented following traditional sequential AF and MLF with free cell starters. The immobilized-cell system, that we here describe for the first time in our knowledge, offers many advantages over conventional free cell fermentations, including: (i) elimination of non-productive cell growth phases; (ii) feasibility of continuous processing; (iii) re-use of the biocatalyst. PMID:27379072

Calculations of absorbed fractions in small water spheres for low-energy monoenergetic electrons and the Auger-emitting radionuclides (123)Ι and (125)Ι.

PubMed

Bousis, Christos; Emfietzoglou, Dimitris; Nikjoo, Hooshang

2012-12-01

To calculate the absorbed fraction (AF) of low energy electrons in small tissue-equivalent spherical volumes by Monte Carlo (MC) track structure simulation and assess the influence of phase (liquid water versus density-scaled water vapor) and of the continuous-slowing-down approximation (CSDA) used in semi-analytic calculations. An event-by-event MC code simulating the transport of electrons in both the vapor and liquid phase of water using appropriate electron-water interaction cross sections was used to quantify the energy deposition of low-energy electrons in spherical volumes. Semi-analytic calculations within the CSDA using a convolution integral of the Howell range-energy expressions are also presented for comparison. The AF for spherical volumes of radii from 10-1000 nm are presented for monoenergetic electrons over the energy range 100-10,000 eV and the two Auger-emitting radionuclides (125)I and (123)I. The MC calculated AF for the liquid phase are found to be smaller than those of the (density scaled) gas phase by up to 10-20% for the monoenergetic electrons and 10% for the two Auger-emitters. Differences between the liquid-phase MC results and the semi-analytic CSDA calculations are up to ∼ 55% for the monoenergetic electrons and up to ∼ 35% for the two Auger-emitters. Condensed-phase effects in the inelastic interaction of low-energy electrons with water have a noticeable but relatively small impact on the AF for the energy range and target sizes examined. Depending on the electron energies, the semi-analytic approach may lead to sizeable errors for target sizes with linear dimensions below 1 micron.

Atrial fibrillation in the Middle East: unmapped, underdiagnosed, undertreated.

PubMed

Al-Shamkhani, Warkaa; Ayetey, Harold; Lip, Gregory Y H

2018-05-01

Atrial fibrillation (AF) is the commonest persistent cardiac arrhythmia with an estimated incidence rate of between 1.5-2% and an important cause of strokes. Few epidemiological studies and clinical trials on the management of AF have been conducted outside Europe and North America. These gaps in our understanding of AF likely lead to sub-optimal management of patients with AF in the rest of the world. Areas covered: We discuss the epidemiology, treatment and clinical outcomes for AF in the Middle East after systematic review of published work for AF from the Middle East. We also discuss important clinical trials on AF conducted in the West in the same period to help contextualize our findings. Expert commentary: The few available Middle East studies suggest important epidemiological differences between Middle Eastern and Western AF populations. In particular, the Middle Eastern AF population is younger and have more co-morbidities than patients in the West. We find that significant numbers of moderate to high risk patients with AF are either undertreated or untreated placing them at increased risk of complications such as stroke. More studies in the Middle Eastern population are required to aid the development of region-specific clinical guidelines to improve patient care.

Persistent atrial fibrillation vs paroxysmal atrial fibrillation: differences in management.

PubMed

Margulescu, Andrei D; Mont, Lluis

2017-08-01

Atrial fibrillation (AF) is the most common human arrhythmia. AF is a progressive disease, initially being nonsustained and induced by trigger activity, and progressing towards persistent AF through alteration of the atrial myocardial substrate. Treatment of AF aims to decrease the risk of stroke and improve the quality of life, by preventing recurrences (rhythm control) or controlling the heart rate during AF (rate control). In the last 20 years, catheter-based and, less frequently, surgical and hybrid ablation techniques have proven more successful compared with drug therapy in achieving rhythm control in patients with AF. However, the efficiency of ablation techniques varies greatly, being highest in paroxysmal and lowest in long-term persistent AF. Areas covered: In this review, we discuss the fundamental differences between paroxysmal and persistent AF and the potential impact of those differences on patient management, emphasizing the available therapeutic strategies to achieve rhythm control. Expert commentary: Treatment to prevent AF recurrences is suboptimal, particularly in patients with persistent AF. Emerging technologies, such as documentation of atrial fibrosis using magnetic resonance imaging and documentation of electrical substrate using advanced electrocardiographic imaging techniques are likely to provide valuable insights about patient-specific tailoring of treatments.

Management of recent-onset sustained atrial fibrillation: pharmacologic and nonpharmacologic strategies.

PubMed

Lau, Dennis H; Kalman, Jonathan; Sanders, Prashanthan

2014-09-01

Recent studies have highlighted significant variations in the management of recent-onset sustained atrial fibrillation (AF). We aim to provide a succinct and clear management algorithm for physicians treating patients with recent-onset sustained AF. We performed a comprehensive search of the literature on the management of recent-onset sustained AF with focus on studies reporting cardioversion of AF, antiarrhythmic agents, and anticoagulation. We also reviewed recent practice guidelines on AF management. This review provides a guide on a tailored management approach of patients with recent-onset sustained AF. After initial detailed clinical assessment, optimal rate and rhythm control options can be provided, depending on hemodynamic stability, duration of AF episode, and AF stroke risk. Issues surrounding electrical and pharmacologic cardioversion are discussed in detail. We emphasize the importance of thromboembolic risk assessment and appropriate anticoagulation surrounding the point of cardioversion. Last, we highlighted the need for appropriate specialized follow-up care after acute AF management. Despite the highly heterogeneous clinical presentations, management of recent-onset sustained AF must include stroke risk assessment, appropriate anticoagulation, and follow-up care in all patients beyond optimum rate and rhythm control strategies. Copyright © 2014. Published by Elsevier Inc.

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

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population.

PubMed

Kim, Daehoon; Yang, Pil-Sung; Jang, Eunsun; Yu, Hee Tae; Kim, Tae-Hoon; Uhm, Jae-Sun; Kim, Jong-Youn; Pak, Hui-Nam; Lee, Moon-Hyoung; Joung, Boyoung; Lip, Gregory Yh

2018-05-01

Most data on the clinical epidemiology of atrial fibrillation (AF) are reported from Western populations, and data for Asians are limited. We aimed to investigate the 10-year trends of the prevalence and incidence of non-valvular AF and provide prevalence projections till 2060 in Korea. We also investigated the annual risks of adverse outcomes among patients with AF. Using the Korean National Health Insurance Service database involving the entire Korean population, a total of 679,416 adults with newly diagnosed AF were identified from 2006 to 2015. The incidence and prevalence of AF and risk of adverse outcomes following AF onset were assessed. The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015. The trend of its incidence was flat with a 10-year overall incidence of 1.77 per 1,000 person-years. The prevalence of AF is expected to reach 5.81% (2,290,591 patients with AF) in 2060. For a decade, the risk of all-cause mortality following AF declined by 30% (adjusted hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.68-0.72), heart failure by 52% (adjusted HR: 0.48, 95% CI: 0.44-0.51), and ischemic stroke by 9% (adjusted HR: 0.91, 95% CI: 0.88-0.93). The burden of AF among Asian patients is increasing. Although the overall risks of cardiovascular events and death following AF onset have decreased over a decade, the event rates are still high. Optimized management of any associated comorbidities should be part of the holistic management approach for patients with AF. Copyright © 2018. Published by Elsevier Inc.

Gibberellic Acid, Synthetic Auxins, and Ethylene Differentially Modulate α-l-Arabinofuranosidase Activities in Antisense 1-Aminocyclopropane-1-Carboxylic Acid Synthase Tomato Pericarp Discs1

PubMed Central

Sozzi, Gabriel O.; Greve, L. Carl; Prody, Gerry A.; Labavitch, John M.

2002-01-01

α-l-Arabinofuranosidases (α-Afs) are plant enzymes capable of releasing terminal arabinofuranosyl residues from cell wall matrix polymers, as well as from different glycoconjugates. Three different α-Af isoforms were distinguished by size exclusion chromatography of protein extracts from control tomatoes (Lycopersicon esculentum) and an ethylene synthesis-suppressed (ESS) line expressing an antisense 1-aminocyclopropane-1-carboxylic synthase transgene. α-Af I and II are active throughout fruit ontogeny. α-Af I is the first Zn-dependent cell wall enzyme isolated from tomato pericarp tissues, thus suggesting the involvement of zinc in fruit cell wall metabolism. This isoform is inhibited by 1,10-phenanthroline, but remains stable in the presence of NaCl and sucrose. α-Af II activity accounts for over 80% of the total α-Af activity in 10-d-old fruit, but activity drops during ripening. In contrast, α-Af III is ethylene dependent and specifically active during ripening. α-Af I released monosaccharide arabinose from KOH-soluble polysaccharides from tomato cell walls, whereas α-Af II and III acted on Na2CO3-soluble pectins. Different α-Af isoform responses to gibberellic acid, synthetic auxins, and ethylene were followed by using a novel ESS mature-green tomato pericarp disc system. α-Af I and II activity increased when gibberellic acid or 2,4-dichlorophenoxyacetic acid was applied, whereas ethylene treatment enhanced only α-Af III activity. Results suggest that tomato α-Afs are encoded by a gene family under differential hormonal controls, and probably have different in vivo functions. The ESS pericarp explant system allows comprehensive studies involving effects of physiological levels of different growth regulators on gene expression and enzyme activity with negligible wound-induced ethylene production. PMID:12114586

Incidence of atrial fibrillation in whites and African-Americans: the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Alonso, Alvaro; Agarwal, Sunil K; Soliman, Elsayed Z; Ambrose, Marietta; Chamberlain, Alanna M; Prineas, Ronald J; Folsom, Aaron R

2009-07-01

To define the incidence and cumulative risk of atrial fibrillation (AF) in a population-based cohort of whites and African Americans. African-Americans reportedly have a lower risk of AF than whites despite their higher exposure to AF risk factors. However, precise estimates of AF incidence in African Americans have not been previously published. We studied the incidence of AF in the Atherosclerosis Risk in Communities (ARIC) study, which has followed up 15,792 men and women 45 to 65 years of age at baseline from 4 communities in the United States since 1987. Atrial fibrillation cases were identified from electrocardiograms conducted at baseline and 3 follow-up visits, and from hospitalizations and death certificates through the end of 2004. During follow-up, 1,085 new cases of AF were identified (196 in African Americans, 889 in whites). Crude incidence rates of AF were 6.7, 4.0, 3.9, and 3.0 per 1,000 persons per year in white men, white women, African-American men, and African-American women, respectively. Increasing age was exponentially associated with an elevated risk of AF. Compared to whites, African-Americans had a 41% (95% CI: 8%-62%) lower age- and sex-adjusted risk of being diagnosed with AF. The cumulative risk of AF at 80 years of age was 21% in white men, 17% in white women, and 11% in African-American men and women. In this population-based cohort, African Americans presented a lower risk of AF than whites. Still, the burden of AF among the former is substantial, with 1 in 9 receiving a diagnosis of AF before 80 years of age.

An epidemiological study on the prevalence of atrial fibrillation in the Chinese population of mainland China.

PubMed

Zhou, Ziqiang; Hu, Dayi

2008-01-01

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Since only limited data on the Chinese population, which is the largest in the world, is available, we conducted an epidemiological study on the prevalence and risk factors of AF in mainland China. This population-based study conducted by cluster sampling comprised 29079 participants forming 14 cohorts from 13 provinces across China, where the population was nearly 1 billion. Every participant underwent electrocardiogram and physical examinations and responded to the interviewer-led questionnaire(s). Univariate and multiple statistical analyses were conducted to explore the relationship between AF prevalence and risk factors. The age-standardized prevalence of AF in China (>or=30 y) was 0.65%, and it increased with age. Men showed a higher prevalence of AF than women (0.91% [age-standardized, 0.66%] vs. 0.65% [0.63%], P = 0.013); several significant risk factors (age, hyperthyroidism, coronary heart disease, and rheumatic heart disease) were identified for AF in the general population. Stroke prevalence was much higher in AF patients than in non-AF people (12.95% vs. 2.28%, P < 0.001). AF was confirmed to be a significant independent risk factor for stroke prevalence in the studied population (OR = 2.776, [1.814, 4.248], P < 0.001). We found that AF patients received poor treatment (2.7%, warfarin; 39.7%, aspirin). This study conducted on a large sample size demonstrates that AF prevalence in mainland China is slightly lower than that in Western countries and similar to that in Asian areas, and confirms that AF is a serious public health problem in China. We identified several potential risk factors, but their associations with AF still need to be further studied.

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.

Predictors of Long-term Success After Concomitant Surgical Ablation for Atrial Fibrillation.

PubMed

Pecha, Simon; Ghandili, Susanne; Hakmi, Samer; Willems, Stephan; Reichenspurner, Hermann; Wagner, Florian Mathias

2017-01-01

According to guidelines, atrial fibrillation (AF) ablation success should be measured by 24-hour Holter electrocardiogram (ECG). However, information on long-term success, especially obtained by 24-hour Holter ECG, is rare. We therefore analyzed rhythm course and long-term outcomes of our patients undergoing concomitant surgical AF ablation. Between January 2003 and April 2011, 486 patients underwent concomitant surgical AF ablation in our institution. Patients with 24-hour Holter ECG rhythm status available between 5 and 10 years postoperatively were included in this retrospective data analysis (n = 155). Ablation lesions were limited to either a pulmonary vein isolation (n = 31, 20%), a more complex left atrial lesion set (n = 89, 57%), or biatrial lesions (n = 35, 23%). Primary end point of the study was freedom from AF during long-term follow-up. Mean patient age was 68.1 ± 8.4 years; 57.4% were male. Mean follow-up time was 5.9 years. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up, with significantly better results in patients with paroxysmal than in those with persistent AF (67.2% vs 51.8% P = 0.03). A stable rhythm course was observed during follow-up, without statistically significant differences between 12 months and latest follow-up (63.2% vs 56.6%; P = 0.25). In multivariate analysis, preoperative paroxysmal AF, duration of AF, and left atrial diameter were predictors of long-term ablation success. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up. Statistically significant predictors of ablation success at latest follow-up were preoperative paroxysmal AF, duration of AF, and a preoperative smaller left atrial diameter. Copyright © 2017. Published by Elsevier Inc.

Comparison of treatment outcomes between convergent procedure and catheter ablation for paroxysmal atrial fibrillation evaluated with implantable loop recorder monitoring.

PubMed

Jan, Matevž; Žižek, David; Geršak, Živa Miriam; Geršak, Borut

2018-05-03

While catheter ablation (CA) is an established treatment for symptomatic paroxysmal atrial fibrillation (AF), convergent epicardial and endocardial ablation procedure (CVP) has been primarily used to treat persistent AF. The aim of this single-center, prospective, randomized study was to compare treatment efficacy of CA and CVP in paroxysmal AF patients by monitoring AF, atrial tachycardia (AT), and atrial flutter (AFL) recurrence with Implantable Loop Recorder (ILR). Fifty patients (74% male) with history of paroxysmal AF were randomized between CA and CVP. Outcomes were determined by ILRs; every episode of AF/AT/AFL lasting 6 minutes or more was defined as a recurrence. AF burden (AFB) and required AF reinterventions (cardioversions and repeat ablations) were quantified after a 3-month blanking period. Total procedural (266 ± 44 vs. 242 ± 39 minutes) and ablation duration (52 ± 10 vs. 48 ± 12 minutes) was similar in both groups. Recurrence of AF/AT/AFL was more likely in the CA group compared to the CVP group (OR 3.78 (95% CI (1.17, 12.19), P  =  0.048)). During the follow-up period (mean 30.5 ± 6.9 months), higher AF burden and more reinterventions for recurrent AF were recorded in the CA group. There were more periprocedural complications in the CVP group (12.5%) compared to the CA group (0%). Treatment of paroxysmal AF with CVP showed less arrhythmia recurrence compared to CA. In addition, patients after CVP had fewer reinterventions and lower AF burden, but more periprocedural complications. © 2018 Wiley Periodicals, Inc.

Atrial Fibrillation and Colonic Neoplasia in African Americans.

PubMed

Nouraie, Mehdi; Kansal, Vandana; Belfonte, Cassius; Ghazvini, Mohammad; Haidari, Tahmineh; Shahnazi, Anahita; Brim, Hassan; Soliman, Elsayed Z; Ashktorab, Hassan

2015-01-01

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American. We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression. The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9-2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7-1.6, P = 0.7) were not significantly associated AF compared to control group. AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.

3D virtual human atria: A computational platform for studying clinical atrial fibrillation.

PubMed

Aslanidi, Oleg V; Colman, Michael A; Stott, Jonathan; Dobrzynski, Halina; Boyett, Mark R; Holden, Arun V; Zhang, Henggui

2011-10-01

Despite a vast amount of experimental and clinical data on the underlying ionic, cellular and tissue substrates, the mechanisms of common atrial arrhythmias (such as atrial fibrillation, AF) arising from the functional interactions at the whole atria level remain unclear. Computational modelling provides a quantitative framework for integrating such multi-scale data and understanding the arrhythmogenic behaviour that emerges from the collective spatio-temporal dynamics in all parts of the heart. In this study, we have developed a multi-scale hierarchy of biophysically detailed computational models for the human atria--the 3D virtual human atria. Primarily, diffusion tensor MRI reconstruction of the tissue geometry and fibre orientation in the human sinoatrial node (SAN) and surrounding atrial muscle was integrated into the 3D model of the whole atria dissected from the Visible Human dataset. The anatomical models were combined with the heterogeneous atrial action potential (AP) models, and used to simulate the AP conduction in the human atria under various conditions: SAN pacemaking and atrial activation in the normal rhythm, break-down of regular AP wave-fronts during rapid atrial pacing, and the genesis of multiple re-entrant wavelets characteristic of AF. Contributions of different properties of the tissue to mechanisms of the normal rhythm and arrhythmogenesis were investigated. Primarily, the simulations showed that tissue heterogeneity caused the break-down of the normal AP wave-fronts at rapid pacing rates, which initiated a pair of re-entrant spiral waves; and tissue anisotropy resulted in a further break-down of the spiral waves into multiple meandering wavelets characteristic of AF. The 3D virtual atria model itself was incorporated into the torso model to simulate the body surface ECG patterns in the normal and arrhythmic conditions. Therefore, a state-of-the-art computational platform has been developed, which can be used for studying multi-scale electrical phenomena during atrial conduction and AF arrhythmogenesis. Results of such simulations can be directly compared with electrophysiological and endocardial mapping data, as well as clinical ECG recordings. The virtual human atria can provide in-depth insights into 3D excitation propagation processes within atrial walls of a whole heart in vivo, which is beyond the current technical capabilities of experimental or clinical set-ups. Copyright © 2011 Elsevier Ltd. All rights reserved.

Atrioventricular node functional remodeling induced by atrial fibrillation.

PubMed

Zhang, Youhua; Mazgalev, Todor N

2012-09-01

The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF. To determine whether AVN undergoes functional remodeling during AF. AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls. Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P <.01), longer AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P <.01), an earlier transition from fast-pathway to SP conduction (at a longer prematurity, 249 ± 60 ms vs 171 ± 24 ms; P <.01), and a slower ventricular rate during simulated AF (RR interval 249 ± 42 ms vs 202 ± 12 ms; P <.01). Notably, a larger proportion of conducted beats utilized the SP in AF preparations (92% ± 12% vs 63% ± 32%; P <.05). Long-term AF in dogs resulted in a longer atrioventricular conduction time and AVN effective refractory period and a slower ventricular rate during AF compared with the controls. Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Central serous chorioretinopathy fundus autofluorescence comparison with two different confocal scanning laser ophthalmoscopes.

PubMed

Nam, Ki Tae; Yun, Cheol Min; Kim, Jee Taek; Yang, Kyung-Sook; Kim, Hyun Joo; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

2015-12-01

To compare the lesion characteristics of two different types of confocal scanning laser ophthalmoscopy (cSLO) autofluorescence (AF) images in central serous chorioretinopathy (CSC). The study included 63 eyes of 61 patients; 63 pairs of fundus autofluorescence (FAF) images were compared before CSC resolution in 63 eyes, FAF images of 31 eyes were also compared after CSC resolution. The lesion characteristics (brightness and composite pattern) were compared between Heidelberg Retina Angiograph 2 (HRA2; Heidelberg Engineering, Germany) and Optomap Tx (Optomap; Optos, Scotland) FAF images. The lesion composite pattern was categorized as diffuse or granular. Diffuse AF was defined as homogenously increased or decreased AF, and granular AF was defined as dot-like, coarse changes in AF. The mean disease duration and subretinal fluid (SRF) height in the spectral domain optical coherence tomography were compared according to the FAF image characteristics. Lesion brightness before CSC resolution was hypo-AF in 48 eyes (76.2 %), hyper-AF in three (4.8 %), and mixed-AF in 12 (19.0 %) in HRA2 FAF images. In comparison, nine (14.3 %) images were hypo-AF, 44 (69.8 %) were hyper-AF, and 10 (15.9 %) were mixed-AF in Optomap FAF images (P < 0.0001). There was no significant difference in lesion composite pattern between the two FAF image wavelengths. Patients with lesions that were hyper-AF in Optomap FAF and hypo-AF in HRA2 FAF had a shorter disease duration and greater SRF height (1 month, 281 um) than those who were hyper-AF in both Optomap and HRA2 images (26 months, 153 um; P = 0.004, 0.001). The two types of FAF images of CSC showed different lesion brightness before and after CSC resolution but demonstrated similar lesion composite patterns.

Study protocol for Smartphone Monitoring for Atrial fibrillation in Real-Time in India (SMART-India): a community-based screening and referral programme

PubMed Central

Karna, Sunil; Patel, Harshil; Fahey, Nisha; Raithatha, Shyamsundar; Handorf, Anna; Bostrom, John; Bashar, Syed; Talati, Kandarp; Shah, Ravi; Goldberg, Robert J; Thanvi, Sunil; Allison, Jeroan J; Chon, Ki; Nimbalkar, Somashekhar Marutirao; McManus, David D

2017-01-01

Introduction Atrial fibrillation (AF), the world’s most common arrhythmia, often goes undetected and untreated in low-resource communities, including India, where AF epidemiology is undefined. AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF. This study aims to describe the epidemiology of AF in Anand District, Gujarat, India, characterise the clinical profile of individuals who are diagnosed with AF and determine the performance of two mobile technologies for community-based AF screening. Methods This observational study builds on findings from a previous feasibility study and leverages two novel technologies as well as an existing community health programme to perform door-to-door AF screening for 2000 people from 60 villages of Anand District, Gujarat, India using local health workers. A single-lead ECG and a pulse-based application is used to screen each individual for AF three times over a period of 5 days. Participants with suspected arrhythmias are followed up by study cardiologist who makes final diagnoses. Participants diagnosed with AF are initiated on treatment based on current anticoagulation guidelines and clinical reasoning. Analytical plan Age-stratified and sex-stratified prevalence of AF in the Anand District will be calculated for sample and estimated for Anand distribution using survey design weights. Sociodemographic and clinical factors associated with AF will be evaluated using multivariable regression methods. Performance of each mobile technology in detecting AF will be evaluated using a 12-lead ECG interpretation as the gold standard. Ethics and dissemination This protocol was approved separately by the Institutional Review Board of University of Massachusetts Medical School and the Human Research Ethics Committee at Charutar Arogya Mandal. The findings of this study will be disseminated through peer-reviewed journals and scientific conferences. PMID:29247089

Treatment of Atrial Fibrillation By The Ablation Of Localized Sources

PubMed Central

Narayan, Sanjiv M.; Krummen, David E.; Shivkumar, Kalyanam; Clopton, Paul; Rappel, Wouter-Jan; Miller, John M.

2012-01-01

Objectives We hypothesized that human atrial fibrillation (AF) may be sustained by localized sources (electrical rotors and focal impulses), whose elimination (Focal Impulse and Rotor Modulation, FIRM) may improve outcome from AF ablation. Background Catheter ablation for AF is a promising therapy, whose success is limited in part by uncertainty in the mechanisms that sustain AF. We developed a computational approach to map whether AF is sustained by several meandering waves (the prevailing hypothesis) or localized sources, then prospectively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome. Methods We recruited 92 individuals during 107 consecutive ablation procedures for paroxysmal or persistent (72%) AF. Cases were prospectively treated, in a 2-arm 1:2 design, by ablation at sources (FIRM-Guided) followed by conventional ablation (n=36), or conventional ablation alone (n=71; FIRM-Blinded). Results Localized rotors or focal impulses were detected in 98 (97%) of 101 cases with sustained AF, each exhibiting 2.1±1.0 sources. The acute endpoint (AF termination or consistent slowing) was achieved in 86% of FIRM-guided versus 20% of FIRM-Blinded cases (p<0.001). FIRM ablation alone at the primary source terminated AF in 2.5 minutes (median; IQR 1.0–3.1). Total ablation time did not differ between groups (57.8±22.8 versus 52.1±17.8 minutes, p=0.16). During 273 days (median; IQR 132–681 days) after a single procedure, FIRM-Guided cases had higher freedom from AF (82.4% versus 44.9%; p<0.001) after a single procedure than FIRM-blinded cases with rigorous, often implanted, ECG monitoring. Adverse events did not differ between groups. CONCLUSIONS Localized electrical rotors and focal impulse sources are prevalent sustaining-mechanisms for human AF. FIRM ablation at patient-specific sources acutely terminated or slowed AF, and improved outcome. These results offer a novel mechanistic framework and treatment paradigm for AF. (ClinicalTrials.gov number, NCT01008722) PMID:22818076

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

Circulating miRNAs in acute new-onset atrial fibrillation and their target mRNA network.

PubMed

da Silva, Ananília Medeiros Gomes; de Araújo, Jéssica Nayara Góes; de Oliveira, Katiene Macêdo; Novaes, Ana Eloísa Melo; Lopes, Mariana Borges; de Sousa, Júlio César Vieira; Filho, Antônio Amorim de Araújo; Luchessi, André Ducati; de Rezende, Adriana Augusto; Hirata, Mário Hiroyuki; Silbiger, Vivian Nogueira

2018-04-20

MicroRNAs (miRNAs) are involved in the pathogenesis of atrial fibrillation (AF), acting on development and progression. Our pilot study investigated the expression of six miRNAs and their miRNA-mRNA interactions in patients with acute new-onset AF, well-controlled AF, and normal sinus rhythm (controls). Plasma of acute new-onset AF patients (n = 5) was collected in the emergency room when patients presented with irregular and fast-atrial fibrillation rhythm. Samples from well-controlled AF (n = 16) and control (n =  15) patients were collected during medical appointments following an ECG. Expression of miR-21, miR-133a, miR-133b, miR-150, miR-328, and miR-499 was analyzed by real-time PCR. Ingenuity Pathway Analysis and the TargetScan database identified the top 30 mRNA targets of these miRNA, seeking the miRNA-mRNA interactions in cardiovascular process. Increased expression of miR-133b (1.4-fold), miR-328 (2.0-fold), and miR-499 (2.3-fold) was observed in patients with acute new-onset AF, compared with well-controlled AF and control patients. Decreased expression of miR-21 was seen in patients with well-controlled AF compared to those with acute new-onset AF and controls (0.6-fold). The miRNA-mRNA interaction demonstrated that SMAD7 and FASLG genes were the targets of miR-21, miR-133b, and miR-499 and were directly related to AF, being involved in apoptosis and fibrosis. The miRNAs had different expression profiles dependent on the AF condition, with higher expression in the acute new-onset AF than well-controlled AF. Clinically, this may contribute to an effective assessment for patients, leading to early detection of AF and monitoring to reduce the risk of other serious cardiovascular events. © 2018 Wiley Periodicals, Inc.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial.

PubMed

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

2015-02-01

Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Patients randomized 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 (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Multimodal Imaging of Disease-Associated Pigmentary Changes in Retinitis Pigmentosa

PubMed Central

Schuerch, Kaspar; Marsiglia, Marcela; Lee, Winston; Tsang, Stephen H.; Sparrow, Janet R.

2016-01-01

Purpose Using multiple imaging modalities we evaluated the changes in photoreceptor cells and RPE that are associated with bone spicule-shaped melanin pigmentation in retinitis pigmentosa (RP). Methods In a cohort of 60 RP patients, short-wavelength autofluorescence (SW-AF), near-infrared (NIR)-AF, NIR-reflectance (NIR-R), spectral domain optical coherence tomography (SD-OCT) and color fundus images were studied. Results Central AF rings were visible in both SW-AF and NIR-AF images. Bone spicule pigmentation was non-reflective in NIR-R, hypoautofluorescent with SW-AF and NIR-AF imaging and presented as intraretinal hyperreflective foci in SD-OCT images. In areas beyond the AF ring outer border, the photoreceptor ellipsoid zone (EZ) band was absent in SD-OCT scans and the visibility of choroidal vessels in SW-AF, NIR-AF and NIR-R images was indicative of reduced RPE pigmentation. Choroidal visibility was most pronounced in the zone approaching peripheral areas of bone spicule pigmentation; here RPE/Bruch’s membrane thinning became apparent in SD-OCT scans. Conclusions These findings are consistent with a process by which RPE cells vacate their monolayer and migrate into inner retina in response to photoreceptor cell degeneration. The remaining RPE spread, undergo thinning and consequently become less pigmented. An explanation for the absence of NIR-AF melanin signal in relation to bone spicule pigmentation is not forthcoming. PMID:28005673

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.

New-onset atrial fibrillation in bacteremia is not associated with C-reactive protein, but is an indicator of increased mortality during hospitalization.

PubMed

Kindem, Ingvild A; Reindal, Eva K; Wester, Astrid L; Blaasaas, Karl G; Atar, Dan

2008-01-01

Several studies have associated elevated C-reactive protein (CRP) levels to the occurrence of atrial fibrillation (AF). We sought to estimate the frequency and prognostic impact of AF in patients with bacteremia, and to study the possible association between AF and CRP as well as between AF and mortality in this population. We retrospectively evaluated patient charts of patients with bacteremia with Escherichia coli or Streptococcus pneumoniae admitted to the Aker University Hospital in Oslo between 1994 and 2004. Known cardiac risk factors for AF, signs and mode of conversion of AF, and, if applicable, date of death were registered, as were characteristics of infection, such as systemic inflammatory response syndrome and white blood cell count. Initial CRP values were categorized into 4 strata. Odds ratios of the 3 highest CRP categories compared with the lowest were obtained from logistic models adjusting for known cardiac risk factors for AF as well as possible factors that may have had an impact on the odds ratios for the different CRP levels. Cox regression analysis was used to compare new-onset AF and death during the first 2 weeks after hospitalization. A total of 672 patient charts were studied; 104 patients (15.4%) had new-onset AF. Peak incidence of new-onset AF occurred on the day of admission. Peak CRP values were reached during the following 2 days. High CRP level at admission did not predict the occurrence of AF. The observed mortality was higher among patients with new-onset AF (p = 0.001) during the first 2 weeks after hospitalization, but this effect disappears when adjusted for relevant factors. The frequency of new-onset AF in bacteremia is substantial. Initial CRP levels or white blood cell count do not seem to predict new-onset AF, as opposed to systemic inflammatory response syndrome. On the other hand, in patients with bacteremia, new-onset AF should be viewed as an indicator of increased mortality and morbidity. Copyright 2008 S. Karger AG, Basel.

Attitudes toward Catheter Ablation for Atrial Fibrillation: A Nationwide Survey among Danish Cardiologists.

PubMed

Vadmann, Henrik; Pedersen, Susanne S; Nielsen, Jens Cosedis; Rodrigo-Domingo, Maria; Pehrson, Steen; Johannessen, Arne; Hansen, Peter Steen; Johansen, Jens Brock; Riahi, Sam

2015-10-01

Catheter ablation for atrial fibrillation (AF) is an important but expensive procedure that is the subject of some debate. Physicians' attitudes toward catheter ablation may influence promotion and patient acceptance. This is the first study to examine the attitudes of Danish cardiologists toward catheter ablation for AF, using a nationwide survey. We developed a purpose-designed questionnaire to evaluate attitudes toward catheter ablation for AF that was sent to all Danish cardiologists (n = 401; response n = 272 (67.8%)). There was no association between attitudes toward ablation and the experience or age of the cardiologist with respect to patients with recurrent AF episodes with a duration of <48 hours or >7 days and/or need for cardioversion. The majority (69%) expected a recurrence of AF after catheter ablation in more than 30% of the cases. For patients with persistent longstanding AF with a duration of >1 year, the attitude toward ablation for longstanding AF was more likely to be positive with increasing age (P < 0.01) and years of experience of the cardiologist (P = 0.002). Danish cardiologists generally have a positive attitude toward catheter ablation for AF, maintain up-to-date knowledge of the procedure, and are aware what information on ablation treatment should be given to patients with AF. The cardiologists had a positive attitude toward ablation for AF in patients with AF episodes <48 hours and patients with episodes >7 days, or those who needed medical/electrical conversion, but a more negative attitude toward treating longstanding AF patients. © 2015 Wiley Periodicals, Inc.

Debris extrusion and foraminal deformation produced by reciprocating instruments made of thermally treated NiTi wires.

PubMed

Frota, Myrna Maria Arcanjo; Bernardes, Ricardo Affonso; Vivan, Rodrigo Ricci; Vivacqua-Gomes, Nilton; Duarte, Marco Antonio Hungaro; Vasconcelos, Bruno Carvalho de

2018-01-18

To evaluate the amount of apically extruded debris, percentage of foraminal enlargement and apical foramen (AF) deformation that occurred during root canal preparation with different reciprocation systems: Reciproc, WaveOne (M-Wire), and ProDesign R (Shape Memory Technology Wire) at two different working lengths (WLs): 0.0 and 1.0 mm beyond the AF. The AF of 120 root canals in 60 mesial roots of mandibular molars were photographed with stereomicroscope and randomly assigned into four groups: manual, Reciproc (REC), WaveOne (WO), and ProDesign R (PDR); subsequently, they were further subdivided according to the WL (n=15). Teeth were instrumented, coupled to a dual collecting chamber, and then another photograph of each AF was captured. Extrusion was analysed by determining the weight of extruded debris. Each AF diameter was measured in pre- and post-instrumentation images to determine deformation, which was analysed, and afterwards the final format of AFs was classified (circular/oval/deformed). We found no significant differences when analysing each system at different WLs. When considering each WL, REC and WO showed highest extrusion values (P<.05); for AF enlargement, differences were observed only for WO, when it was used beyond the AF; differences were observed among M-Wire groups beyond the AF (P<.05). AF deformation was observed in all groups; PDR showed the lowest AF deformation values at both WLs; M-Wire groups showed 50% strain beyond the AF. Authors concluded that beyond the apical limit, the alloy and taper are important aspects when considering extrusion and deformation.

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.

Incidence, predictive factors, management, and survival impact of atrial fibrillation in non-Hodgkin lymphoma.

PubMed

Sorigue, Marc; Gual-Capllonch, Francisco; Garcia, Olga; Sarrate, Edurne; Franch-Sarto, Mireia; Ibarra, Gladys; Grau, Javier; Orna, Elisa; Ribera, Josep-Maria; Sancho, Juan-Manuel

2018-05-04

Atrial fibrillation (AF) and cancer are common disorders in the general population but there are few studies in patients with both diseases. More specifically, there are scarce data on AF in patients with non-Hodgkin lymphoma (NHL). We assessed the incidence, predictive factors, management, and survival impact of AF in a cohort of patients with NHL from a single institution between 2002 and 2016 (n = 747). Twenty-three patients were diagnosed with AF before and 40 after the diagnosis of NHL (of the later, 16 were secondary to an extracardiac comorbidity and 24 unrelated to any triggering event [primary AF]). The 5-year cumulative incidence of new-onset AF was 4% (95% confidence interval [CI] 3-6%). Age and hypertension were the only predictive factors for the development of AF. Management of AF was heterogeneous, primarily with anti-vitamin K agents but also antiplatelet therapy in a significant proportion of patients. Among the 63 patients, there were six episodes of ischemic stroke/transient ischemic attack and four venous thromboembolic events, with four major bleeding episodes. Overall survival (OS) was inferior in patients with AF (HR 0.1, 95% CI 0.01-0.7, p = 0.02), largely due to secondary AF. We conclude that the incidence of new-onset AF in NHL patients seemed somewhat higher than in the general population, although with similar predictive factors. The management was heterogeneous, and the risk of ischemic and hemorrhagic events did not seem higher than in cancer-free patients. Survival was particularly poor for patients with secondary AF.

Recurrence quantification analysis applied to spatiotemporal pattern analysis in high-density mapping of human atrial fibrillation.

PubMed

Zeemering, Stef; Bonizzi, Pietro; Maesen, Bart; Peeters, Ralf; Schotten, Ulrich

2015-01-01

Spatiotemporal complexity of atrial fibrillation (AF) patterns is often quantified by annotated intracardiac contact mapping. We introduce a new approach that applies recurrence plot (RP) construction followed by recurrence quantification analysis (RQA) to epicardial atrial electrograms, recorded with a high-density grid of electrodes. In 32 patients with no history of AF (aAF, n=11), paroxysmal AF (PAF, n=12) and persistent AF (persAF, n=9), RPs were constructed using a phase space electrogram embedding dimension equal to the estimated AF cycle length. Spatial information was incorporated by 1) averaging the recurrence over all electrodes, and 2) by applying principal component analysis (PCA) to the matrix of embedded electrograms and selecting the first principal component as a representation of spatial diversity. Standard RQA parameters were computed on the constructed RPs and correlated to the number of fibrillation waves per AF cycle (NW). Averaged RP RQA parameters showed no correlation with NW. Correlations improved when applying PCA, with maximum correlation achieved between RP threshold and NW (RR1%, r=0.68, p <; 0.001) and RP determinism (DET, r=-0.64, p <; 0.001). All studied RQA parameters based on the PCA RP were able to discriminate between persAF and aAF/PAF (DET persAF 0.40 ± 0.11 vs. 0.59 ± 0.14/0.62 ± 0.16, p <; 0.01). RP construction and RQA combined with PCA provide a quick and reliable tool to visualize dynamical behaviour and to assess the complexity of contact mapping patterns in AF.

Influence of atrial substrate on local capture induced by rapid pacing of atrial fibrillation.

PubMed

Rusu, Alexandru; Jacquemet, Vincent; Vesin, Jean-Marc; Virag, Nathalie

2014-05-01

Preliminary studies showed that the septum area was the only location allowing local capture of both the atria during rapid pacing of atrial fibrillation (AF) from a single site. The present model-based study investigated the influence of atrial substrate on the ability to capture AF when pacing the septum. Three biophysical models of AF with an identical anatomy from human atria but with different AF substrates were used: (i) AF based on multiple wavelets, (ii) AF based on heterogeneities in vagal activation, (iii) AF based on heterogeneities in repolarization. A fourth anatomical model without Bachmann's bundle (BB) was also implemented. Rapid pacing was applied from the septum at pacing cycle lengths in the range of 50-100% of AF cycle length. Local capture was automatically assessed with 24 pairs of electrodes evenly distributed on the atrial surface. The results were averaged over 16 AF simulations. In the homogeneous substrate, AF capture could reach 80% of the atrial surface. Heterogeneities degraded the ability to capture during AF. In the vagal substrate, the capture tended to be more regular and the degradation of the capture was not directly related to the spatial extent of the heterogeneities. In the third substrate, heterogeneities induced wave anchorings and wavebreaks even in areas close to the pacing site, with a more dramatic effect on AF capture. Finally, BB did not significantly affect the ability to capture. Atrial fibrillation substrate had a significant effect on rapid pacing outcomes. The response to therapeutic pacing may therefore be specific to each patient.

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.

Impact of atrial fibrillation on stroke-related healthcare costs.

PubMed

Sussman, Matthew; Menzin, Joseph; Lin, Iris; Kwong, Winghan J; Munsell, Michael; Friedman, Mark; Selim, Magdy

2013-11-25

Limited data exist on the economic implications of stroke among patients with atrial fibrillation (AF). This study assesses the impact of AF on healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS), or transient ischemic attack (TIA). A retrospective analysis of MarketScan claims data (2005-2011) for AF patients ≥18 years old with ≥1 inpatient claim for stroke, or ≥1 ED or inpatient claim for TIA as identified by ICD-9-CM codes who had ≥12 months continuous enrollment prior to initial stroke. Initial event- and stroke-related costs 12 months post-index were compared among patients with AF and without AF. Adjusted costs were estimated, controlling for demographics, comorbidities, anticoagulant use, and baseline resource use. Data from 23,807 AF patients and 136,649 patients without AF were analyzed. Unadjusted mean cost of the index event was $20,933 for IS, $59,054 for HS, $8616 for TIA hospitalization, and $3395 for TIA ED visit. After controlling for potential confounders, adjusted mean incremental costs (index plus 12-month post-index) for AF patients were higher than those for non-AF patients by: $4726, $7824, and $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and $1700 for TIA (identified by ED) (all P<0.01). In multivariate regression analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in total stroke-related costs. Stroke-related care for IS, HS, and TIA is costly, especially among individuals with AF. Reducing the risk of AF-related stroke is important from both clinical and economic standpoints.

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

[Structural and functional changes of myocardium in Chernobyl disaster clean-up workers with atrial fibrillation].

PubMed

Khomaziuk, I M; Habulavichene, Zh M; Khomaziuk, V A

2011-01-01

Particularities and clinical importance of the structural and functional changes of myocardium were estimated in Chernobyl disaster clean-up workers with atrial fibrillation (AF). We examined 122 men with AF, which was associated with ischemic heart disease and arterial hypertension. Paroxysmal AF was diagnosed in 42 patients, 80 patients had permanent AE Control group comprised 80 men without AF. Echocardiography and Doppler studies were performed using ultrasound scanner Aloka SSD-630 (Japan). Significant structural and functional changes of the heart were revealed already in paroxysmal AF and became more pronounced in permanent AF. Increased left atrial size, its ratio to left ventricular end diastolic diameter, diastolic dysfunction were important echocardiographic predictors of AF. Heart walls thickening was accompanied by disorders of myocardial relaxation, increase in myocardial mass led to ischemia, and together they promoted overload, dysfunction of atrium and development of AF. Obligatory echocardiographic examination of the Chernobyl disaster clean-up workers with ischemic heart disease and arterial hypertension is necessary for predicting AF early, ordering adequate therapy in proper time and improving prognosis.

Supplier Development: A Long-Term Supportability Option For USAF Engines

DTIC Science & Technology

2012-02-01

Supply Chain Management Practices..................8 AF and DoD Regulations "Limitation or Hoax" Can USAF Develop Suppliers...integrated supply chain management (SCM) process providing engines and parts, aiding in the ability of the depots to meet the warfighter‟s needs. The... supply chain has struggled in the past to support the warfighter with enough engines to accomplish the mission. The engine supply chain management

Multimedia-Based Integration of Cross-Layer Techniques

DTIC Science & Technology

2014-06-01

wireless networks play a critical role in net-centric warfare, including the sharing of the time-sensitive battlefield information among military nodes for...layer protocols are key enablers in effectively deploying the military wireless network. This report discusses the design of cross-layer protocols...2 1.0 INTRODUCTION 1.1 Motivation The Air Force (AF) Wireless Networks (also denoted as military networks in this report) must be capable of

Predisposing factors for atrial fibrillation in the elderly

PubMed Central

Wasmer, Kristina; Eckardt, Lars; Breithardt, Günter

2017-01-01

Atrial fibrillation (AF) in the elderly occurs as a consequence of cardiovascular aging and an age related increase of comorbidity. Several predisposing factors for AF have been identified for the overall AF population. Most of them, cardiovascular disease in particular, play a role in younger and older patients. The longer time period during which these risk factors can cause structural changes that ultimately lead to AF may, at least in part, explain the association between age and AF. In addition, less well defined age-related changes in cellular electrophysiologic properties and structure predispose to AF in the elderly. PMID:28592961

Characterization of a novel antibacterial glycopeptide produced by Penicillium sp. M03.

PubMed

Yang, W H; Zhang, W C; Lu, X M; Jiang, G S; Gao, P J

2009-04-01

To isolate a novel antibiotic termed AF from fermentation broth of Penicillium sp. M03 and to examine its antimicrobial activity, biological properties and structure characteristics. Sephadex LH-20 and HPLC were used to purify AF from fermentation broth of Penicillium sp. M03. The antimicrobial activity of AF was evaluated with the agar diffusion test. Amino acid and monosaccharide composition of AF was analysed by a HITACHI 835 detector and HPLC assay, respectively. Matrix-assisted laser desorption time of flight mass spectrometry, FT-IR and (1)H nuclear magnetic resonance spectra analyses were performed to examine the initial structure of AF. Eighty milligrams of AF was isolated as white powder from 1-l Penicillium sp. M03 fermentation broth. It consists of five amino acid and two monosaccharide residues and the molecular weight of it was 1017, and it was stable to beta-lactamase, heat, acid and alkali. AF showed inhibitory activity to a wide range of bacteria, particularly to multidrug-resistant Staphylococcus aureus. AF was a novel antibacterial glycopeptide with a broad inhibitory spectrum to pathogenic bacteria including multidrug-resistant agents. Furthermore, it is difficult to generate bacteria resistant to AF. Characterization of AF made it a potential antibiotic to fight against antibiotic-resistant bacterial pathogens.

A new predictor of atrial fibrillation after coronary artery bypass graft surgery: HATCH score.

PubMed

Selvi, Mithat; Gungor, Hasan; Zencir, Cemil; Gulasti, Sevil; Eryilmaz, Ufuk; Akgullu, Cagdas; Durmaz, Selim

2018-03-01

The aim of this study was to investigate the association between HATCH score and atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. 369 patients (103 patients with AF and 266 patients without AF) undergoing isolated CABG surgery were analyzed. Complete medical records were retrospectively collected to investigate HATCH score. The median age of patients with AF was significantly higher than the median age of non-AF group (60.8±10.0 years vs 67.8±9.5 years, P<0.001). HATCH score was significantly higher in patients who developed AF after CABG surgery than the non-AF group (P=0.017). Multivariate logistic regression analysis showed that HATCH score (OR 1.334; 95% CI 1.022 to 1.741, P=0.034) was an independent predictor of AF after CABG surgery. Receiver operating characteristic curve analysis showed that the cut-off point of HATCH score related to predict AF was >1 (two or more), with a sensitivity of 42% and specificity of 70%. Patients with elevated preoperative HATCH score may have higher risk for AF after CABG surgery. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Atrial Fibrillation in Eight New World Camelids.

PubMed

Bozorgmanesh, R; Magdesian, K G; Estell, K E; Stern, J A; Swain, E A; Griffiths, L G

2016-01-01

There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). Describe clinical signs and outcome of AF in NWC. Eight New World Camelids admitted with AF. A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Quantitative fundus autofluorescence in healthy eyes.

PubMed

Greenberg, Jonathan P; Duncker, Tobias; Woods, Russell L; Smith, R Theodore; Sparrow, Janet R; Delori, François C

2013-08-21

Fundus autofluorescence was quantified (qAF) in subjects with healthy retinae using a standardized approach. The objective was to establish normative data and identify factors that influence the accumulation of RPE lipofuscin and/or modulate the observed AF signal in fundus images. AF images were acquired from 277 healthy subjects (age range: 5-60 years) by employing a Spectralis confocal scanning laser ophthalmoscope (cSLO; 488-nm excitation; 30°) equipped with an internal fluorescent reference. For each image, mean gray level was calculated as the average of eight preset regions, and was calibrated to the reference, zero-laser light, magnification, and optical media density from normative data on lens transmission spectra. Relationships between qAF and age, sex, race/ethnicity, eye color, refraction/axial length, and smoking status were evaluated as was measurement repeatability and the qAF spatial distribution. qAF levels exhibited a significant increase with age. qAF increased with increasing eccentricity up to 10° to 15° from the fovea and was highest superotemporally. qAF values were significantly greater in females, and, compared with Hispanics, qAF was significantly higher in whites and lower in blacks and Asians. No associations with axial length and smoking were observed. For two operators, between-session repeatability was ± 9% and ± 12%. Agreement between the operators was ± 13%. Normative qAF data are a reference tool essential to the interpretation of qAF measurements in ocular disease.

Clinical, Electrocardiographic, and Echocardiographic Parameter Combination Predicts the Onset of Atrial Fibrillation.

PubMed

Soeki, Takeshi; Matsuura, Tomomi; Tobiume, Takeshi; Bando, Sachiko; Matsumoto, Kazuhisa; Nagano, Hiromi; Uematsu, Etsuko; Kusunose, Kenya; Ise, Takayuki; Yamaguchi, Koji; Yagi, Shusuke; Fukuda, Daiju; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Sata, Masataka

2018-05-30

The ability to identify risk markers for new-onset atrial fibrillation (AF) is critical to the development of preventive strategies, but it remains unknown whether a combination of clinical, electrocardiographic, and echocardiographic parameters predicts the onset of AF. In the present study, we evaluated the predictive value of a combined score that includes these parameters.Methods and Results:We retrospectively studied 1,040 patients without AF who underwent both echocardiography and 24-h Holter electrocardiography between May 2005 and December 2010. During a median follow-up period of 68.4 months (IQR, 49.9-93.3 months), we investigated the incidence of new-onset AF. Of the 1,040 patients, 103 (9.9%) developed AF. Patients who developed AF were older than patients who did not. Total heart beats, premature atrial contraction (PAC) count, maximum RR interval, and frequency of sinus pause quantified on 24-h electrocardiography were associated with new-onset AF. LA diameter (LAD) on echocardiography was also associated with the development of AF. On multivariate Cox analysis, age ≥58 years, PAC count ≥80 beats/day, maximum RR interval ≥1.64 s, and LAD ≥4.5 cm were independently associated with the development of AF. The incidence rate of new-onset AF significantly increased as the combined score (i.e., the sum of the risk score determined using hazard ratios) increased. A combined score that includes age, PAC count, maximum RR interval, and LAD could help characterize the risk of new-onset AF.

Statin and Atrial Fibrilation: When does it work?

PubMed

Fauchier, Laurent; Clementy, Nicolas; Pierre, Bertrand; Babuty, Dominique

2012-01-01

In the recent years, some clinical and experimental studies have suggested that the use of statins may protect against atrial fibrillation (AF). A relation between inflammation and the development of AF has been described, and the potent anti-inflammatory and antioxidant properties of statins may make them effective in preventing the development of AF. A global analysis of the literature suggests that the use of statins is associated with a decreased risk of incidence or recurrence of AF in some cases. However, this beneficial effect is not seen for all types of AF in all the patients. The use of statins seems associated 1) with a lack of benefit in primary prevention of AF, 2) with a significant but heterogeneous decreased risk of recurrence of AF in secondary prevention, and 3) with a very significant and homogeneous reduction for the risk of post operative AF. An intensive lipid lowering statin regimen does not provide greater protection against AF. Patients with coronary heart disease are curr ently treated with statins in most cases, and this may not have an impact on their treatment. In contrast, it remains to determine more accurately if statins may bring a significant benefit for some AF patients without any type of established atherosclerotic disease or with a low risk of atherogenesis. Since it remains uncertain whether the suppression of AF in these patients is beyond doubt beneficial, prescribing statins for this purpose alone should not be recommended at the present time.

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.

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

The lateralized arcuate fasciculus in developmental pitch disorders among mandarin amusics: left for speech and right for music.

PubMed

Chen, Xizhuo; Zhao, Yanxin; Zhong, Suyu; Cui, Zaixu; Li, Jiaqi; Gong, Gaolang; Dong, Qi; Nan, Yun

2018-05-01

The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech and music development. Although the predominant role of the left AF in speech development is relatively clear, how the AF engages in music development is not understood. Congenital amusia is a special neurodevelopmental condition, which not only affects musical pitch but also speech tone processing. Using diffusion tensor tractography, we aimed at understanding the role of AF in music and speech processing by examining the neural connectivity characteristics of the bilateral AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)-matched controls, amusics demonstrated increased connectivity as reflected by the increased fractional anisotropy in the right posterior AF but decreased connectivity as reflected by the decreased volume in the right anterior AF. Moreover, greater fractional anisotropy in the left direct AF was correlated with worse performance in speech tone perception among amusics. This study is the first to examine the neural connectivity of AF in the neurodevelopmental condition of amusia as a result of disrupted music pitch and speech tone processing. We found abnormal white matter structural connectivity in the right AF for the amusic individuals. Moreover, we demonstrated that the white matter microstructural properties of the left direct AF is modulated by lexical tone deficits among the amusic individuals. These data support the notion of distinctive pitch processing systems between music and speech.

Expression of TGFbeta1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs.

PubMed

Li, Shufeng; Li, Hongli; Mingyan, E; Yu, Bo

2009-02-01

The development of pulmonary vein stenosis has recently been described after radiofrequency ablation (RF) to treat atrial fibrillation (AF). The purpose of this study was to examine expression of TGFbeta1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs. About 28 mongrel dogs were randomly assigned to the sham-operated group (n = 7), the AF group (n = 7), AF + RF group (n = 7), and RF group (n = 7). In AF or AF + RF groups, dogs underwent chronic pulmonary vein (PV) pacing to induce sustained AF. RF application was applied around the PVs until electrical activity was eliminated. Histological assessment of pulmonary veins was performed using hematoxylin and eosin staining; TGFbeta1 gene expression in pulmonary veins was examined by RT-PCR analysis; expression of TGFbeta1 protein in pulmonary veins was assessed by Western blot analysis. Rapid pacing from the left superior pulmonary vein (LSPV) induced sustained AF in AF group and AF + RF group. Pulmonary vein ablation terminated the chronic atrial fibrillation in dogs. Histological examination revealed necrotic tissues in various stages of collagen replacement, intimal thickening, and cartilaginous metaplasia with chondroblasts and chondroclasts. Compared with sham-operated and AF group, TGFbeta1 gene and protein expressions was increased in AF + RF or RF groups. It was concluded that TGFbeta1 might be associated with pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs.

Correction of autofluorescence intensity for epithelial scattering by optical coherence tomography: a phantom study

NASA Astrophysics Data System (ADS)

Pahlevaninezhad, H.; Lee, A. M. D.; Hyun, C.; Lam, S.; MacAulay, C.; Lane, P. M.

2013-03-01

In this paper, we conduct a phantom study for modeling the autofluorescence (AF) properties of tissue. A combined optical coherence tomography (OCT) and AF imaging system is proposed to measure the strength of the AF signal in terms of the scattering layer thickness and concentration. The combined AF-OCT system is capable of estimating the AF loss due to scattering in the epithelium using the thickness and scattering concentration calculated from the co-registered OCT images. We define a correction factor to account for scattering losses in the epithelium and calculate a scatteringcorrected AF signal. We believe the scattering-corrected AF will reduce the diagnostic false-positives rate in the early detection of airway lesions due to confounding factors such as increased epithelial thickness and inflammations.

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-β1

PubMed Central

Davies, Christopher J.; Regouski, Misha; Hall, Justin; Olsen, Aaron L.; Meng, Qinggang; Rutigliano, Heloisa M.; Dosdall, Derek J.; Angel, Nathan A.; Sachse, Frank B.; Seidel, Thomas; Thomas, Aaron J.; Stott, Rusty; Panter, Kip E.; Lee, Pamela M.; Van Wettere, Arnaud J.; Stevens, John R.; Wang, Zhongde; MacLeod, Rob S.; Marrouche, Nassir F.; White, Kenneth L.

2016-01-01

Introduction Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF. Methods and Results Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12-month of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas, none of 6 controls displayed sustained AF (P<0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687±212.02 vs. 2.50±0.88 seconds, P<0.0001), but no persistent or permanent AF was observed. Conclusion A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility. PMID:27447370

Association between Heat Shock Protein-60 and Development of Atrial Fibrillation: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Maan, Abhishek; Jorgensen, Neal W; Mansour, Moussa; Dudley, Samuel; Jenny, Nancy S; Defilippi, Christopher; Szklo, Moyses; Alonso, Alvaro; Refaat, Marwan M; Ruskin, Jeremy; Heckbert, Susan R; Heist, E Kevin

2016-12-01

During atrial fibrillation (AF), a high rate of myocyte activation causes cellular stress and initiates the process of atrial remodeling, which further promotes persistence of AF. Although heat shock proteins (HSPs) have been shown to prevent atrial remodeling and suppress the occurrence of AF in cellular and animal experimental models, increased levels of HSP-60 have been observed in patients with postoperative AF, likely reflecting a response to cellular stress. To better understand the role of HSP-60 in relation to AF, we examined the association of HSP-60 levels in relation to the future development of AF in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a cohort study that recruited 6,814 participants aged 45-84 years and free of known cardiovascular disease at baseline (2000-2002) from six field centers. We investigated 983 participants, selected at random from the total cohort, who had HSP-60 measured and were free of AF at baseline. We tested the association of HSP-60 levels with the incidence of AF using multivariate Cox models after adjustment for demographics, clinical characteristics, and biomarkers. During an average of 10.6 years of follow-up, 77 participants developed AF. We did not observe a significant association between the log-transformed HSP-60 levels and development of AF on either unadjusted or multivariate analysis (adjusted hazard ratio: 1.02 per unit difference on natural log scale, 95% confidence interval: 0.77-1.34 ln (ng/mL). Contrary to the findings from the preclinical studies, which demonstrated an important role of HSP-60 in the pathogenesis of AF, we did not observe a significant association between HSP-60 and occurrence of AF. © 2016 Wiley Periodicals, Inc.

Pulmonary Vein Isolation Alone Versus Additional Linear Ablation in Patients With Persistent Atrial Fibrillation Converted to Paroxysmal Type With Antiarrhythmic Drug Therapy: A Multicenter, Prospective, Randomized Study.

PubMed

Yu, Hee Tae; Shim, Jaemin; Park, Junbeom; Kim, In-Soo; Kim, Tae-Hoon; Uhm, Jae-Sun; Joung, Boyoung; Lee, Moon-Hyoung; Kim, Young-Hoon; Pak, Hui-Nam

2017-06-01

Atrial fibrillation (AF) type can vary depending on condition and timing, and some patients who initially present with persistent AF may be changed to paroxysmal AF after antiarrhythmic drug medication and cardioversion. We investigated whether circumferential pulmonary vein isolation (CPVI) alone is an effective rhythm control strategy in patients with persistent AF to paroxysmal AF. We enrolled 113 patients with persistent AF to paroxysmal AF (male 75%, 60.4±10.1 years old) who underwent catheter ablation for nonvalvular AF at 3 tertiary hospitals. The participants were randomly assigned to 2 groups: CPVI alone (n=59) or CPVI plus linear ablation (CPVI+Line; posterior box+anterior line, n=54). Compared with the CPVI+Line, CPVI alone required shorter procedure (187.2±58.0 versus 211.2±63.9 min; P =0.043) and ablation times (4922.1±1110.5 versus 6205.7±1425.2 s; P <0.001) without difference in procedure-related major complication (3% versus 2%; P =0.611). Antiarrhythmic drug utility rates after ablation were not different between the 2 groups (22% versus 30%; P =0.356). Overall, AF-free survival (log-rank; P =0.206) and AF and antiarrhythmic drug-free survival (log-rank; P =0.321) were not different between groups. CPVI alone is an effective rhythm control strategy with a shorter procedure time in persistent AF patients converted to paroxysmal AF compared with CPVI with linear ablation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02176616. © 2017 American Heart Association, Inc.

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.

Strict sequential catheter ablation strategy targeting the pulmonary veins and superior vena cava for persistent atrial fibrillation.

PubMed

Yoshiga, Yasuhiro; Shimizu, Akihiko; Ueyama, Takeshi; Ono, Makoto; Fukuda, Masakazu; Fumimoto, Tomoko; Ishiguchi, Hironori; Omuro, Takuya; Kobayashi, Shigeki; Yano, Masafumi

2018-08-01

An effective catheter ablation strategy, beyond pulmonary vein isolation (PVI), for persistent atrial fibrillation (AF) is necessary. Pulmonary vein (PV)-reconduction also causes recurrent atrial tachyarrhythmias. The effect of the PVI and additional effect of a superior vena cava (SVC) isolation (SVCI) was strictly evaluated. Seventy consecutive patients with persistent AF who underwent a strict sequential ablation strategy targeting the PVs and SVC were included in this study. The initial ablation strategy was a circumferential PVI. A segmental SVCI was only applied as a repeat procedure when patients demonstrated no PV-reconduction. After the initial procedure, persistent AF was suppressed in 39 of 70 (55.7%) patients during a median follow-up of 32 months. After multiple procedures, persistent AF was suppressed in 46 (65.7%) and 52 (74.3%) patients after receiving the PVI alone and PVI plus SVCI strategies, respectively. In 6 of 15 (40.0%) patients with persistent AF resistant to PVI, persistent AF was suppressed. The persistent AF duration independently predicted persistent AF recurrences after multiple PVI alone procedures [HR: 1.012 (95% confidence interval: 1.006-1.018); p<0.001] and PVI plus SVCI strategies [HR: 1.018 (95% confidence interval: 1.011-1.025); p<0.001]. A receiver-operating-characteristic analysis for recurrent persistent AF indicated an optimal cut-off value of 20 and 32 months for the persistent AF duration using the PVI alone and PVI plus SVCI strategies, respectively. The outcomes of the PVI plus SVCI strategy were favorable for patients with shorter persistent AF durations. The initial SVCI had the additional effect of maintaining sinus rhythm in some patients with persistent AF resistant to PVI. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified

PubMed Central

Movérare-Skrtic, Sofia; Börjesson, Anna E.; Farman, Helen H.; Sjögren, Klara; Windahl, Sara H.; Lagerquist, Marie K.; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

2014-01-01

The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-20) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-20 mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-20 mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. PMID:24395795

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified.

PubMed

Movérare-Skrtic, Sofia; Börjesson, Anna E; Farman, Helen H; Sjögren, Klara; Windahl, Sara H; Lagerquist, Marie K; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

2014-01-21

The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-2(0)) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-2(0) mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-2(0) mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist.

Debris extrusion and foraminal deformation produced by reciprocating instruments made of thermally treated NiTi wires

PubMed Central

Frota, Myrna Maria Arcanjo; Bernardes, Ricardo Affonso; Vivan, Rodrigo Ricci; Vivacqua-Gomes, Nilton; Duarte, Marco Antonio Hungaro; de Vasconcelos, Bruno Carvalho

2018-01-01

Abstract Objective To evaluate the amount of apically extruded debris, percentage of foraminal enlargement and apical foramen (AF) deformation that occurred during root canal preparation with different reciprocation systems: Reciproc, WaveOne (M-Wire), and ProDesign R (Shape Memory Technology Wire) at two different working lengths (WLs): 0.0 and 1.0 mm beyond the AF. Material and methods The AF of 120 root canals in 60 mesial roots of mandibular molars were photographed with stereomicroscope and randomly assigned into four groups: manual, Reciproc (REC), WaveOne (WO), and ProDesign R (PDR); subsequently, they were further subdivided according to the WL (n=15). Teeth were instrumented, coupled to a dual collecting chamber, and then another photograph of each AF was captured. Extrusion was analysed by determining the weight of extruded debris. Each AF diameter was measured in pre- and post-instrumentation images to determine deformation, which was analysed, and afterwards the final format of AFs was classified (circular/oval/deformed). Results We found no significant differences when analysing each system at different WLs. When considering each WL, REC and WO showed highest extrusion values (P<.05); for AF enlargement, differences were observed only for WO, when it was used beyond the AF; differences were observed among M-Wire groups beyond the AF (P<.05). AF deformation was observed in all groups; PDR showed the lowest AF deformation values at both WLs; M-Wire groups showed 50% strain beyond the AF. Conclusion Authors concluded that beyond the apical limit, the alloy and taper are important aspects when considering extrusion and deformation. PMID:29364346

Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults with Chronic Kidney Disease

PubMed Central

Bansal, Nisha; Fan, Dongjie; Hsu, Chi-yuan; Ordonez, Juan D.; Marcus, Gregory M.; Go, Alan S.

2013-01-01

Background Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. Methods and Results We studied adults with CKD (defined as persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002–2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206,229 adults with CKD, 16,463 developed incident AF. During a mean follow-up of 5.1± 2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) compared with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in rate of ESRD (hazard ratio 1.67, 95% confidence interval: 1.46–1.91). Conclusions Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD. PMID:23275377

Temporal trends in the occurrence and outcomes of atrial fibrillation in patients with acute myocardial infarction (from the Atherosclerosis Risk in Communities Surveillance Study).

PubMed

Bengtson, Lindsay G S; Chen, Lin Y; Chamberlain, Alanna M; Michos, Erin D; Whitsel, Eric A; Lutsey, Pamela L; Duval, Sue; Rosamond, Wayne D; Alonso, Alvaro

2014-09-01

Atrial fibrillation (AF) frequently coexists in the setting of myocardial infarction (MI), being associated with increased mortality. Nonetheless, temporal trends in the occurrence of AF complicating MI and in the prognosis of these patients are not well described. We examined temporal trends in prevalence of AF in the setting of MI and the effect of AF on prognosis in the community. We studied a population-based sample of 20,049 validated first-incident nonfatal hospitalized MIs among 35- to 74-year old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 2009. Prevalence of AF in the setting of MI increased from 11% to 15% during the 23-year study period. The multivariable adjusted odds ratio for prevalent AF, per 5-year increment, was 1.11 (95% confidence interval 1.04 to 1.19). Overall, in patients with MI, AF was associated with increased 1-year case fatality (odds ratio 1.47, 95% confidence interval 1.07 to 2.01) compared with those without AF. However, there was no evidence that the impact of AF on MI survival changed over time or differed over time by sex, race, or MI classification (all p values >0.10). In conclusion, co-occurrence of AF in MI slightly increased between 1987 and 2009. The adverse impact of AF on survival in the setting of MI was consistent throughout. In the setting of MI, co-occurrence of AF should be viewed as a critical clinical event, and treatment needs unique to this population should be explored further. Copyright © 2014 Elsevier Inc. All rights reserved.

Dominant frequency increase rate predicts transition from paroxysmal to long-term persistent atrial fibrillation.

PubMed

Martins, Raphael P; Kaur, Kuljeet; Hwang, Elliot; Ramirez, Rafael J; Willis, B Cicero; Filgueiras-Rama, David; Ennis, Steven R; Takemoto, Yoshio; Ponce-Balbuena, Daniela; Zarzoso, Manuel; O'Connell, Ryan P; Musa, Hassan; Guerrero-Serna, Guadalupe; Avula, Uma Mahesh R; Swartz, Michael F; Bhushal, Sandesh; Deo, Makarand; Pandit, Sandeep V; Berenfeld, Omer; Jalife, José

2014-04-08

Little is known about the mechanisms underlying the transition from paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long-standing persistent AF we tested the hypothesis that the rate of electric and structural remodeling, assessed by dominant frequency (DF) changes, determines the time at which AF becomes persistent. Self-sustained AF was induced by atrial tachypacing. Seven sheep were euthanized 11.5±2.3 days after the transition to persistent AF and without reversal to sinus rhythm; 7 sheep were euthanized after 341.3±16.7 days of long-standing persistent AF. Seven sham-operated animals were in sinus rhythm for 1 year. DF was monitored continuously in each group. Real-time polymerase chain reaction, Western blotting, patch clamping, and histological analyses were used to determine the changes in functional ion channel expression and structural remodeling. Atrial dilatation, mitral valve regurgitation, myocyte hypertrophy, and atrial fibrosis occurred progressively and became statistically significant after the transition to persistent AF, with no evidence for left ventricular dysfunction. DF increased progressively during the paroxysmal-to-persistent AF transition and stabilized when AF became persistent. Importantly, the rate of DF increase correlated strongly with the time to persistent AF. Significant action potential duration abbreviation, secondary to functional ion channel protein expression changes (CaV1.2, NaV1.5, and KV4.2 decrease; Kir2.3 increase), was already present at the transition and persisted for 1 year of follow up. In the sheep model of long-standing persistent AF, the rate of DF increase predicts the time at which AF stabilizes and becomes persistent, reflecting changes in action potential duration and densities of sodium, L-type calcium, and inward rectifier currents.

Socioeconomic status and the development of 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; Ferrick, Kevin J; Krumerman, Andrew

2017-09-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with significant morbidity and mortality. Despite having a higher burden of traditional AF risk factors, African American and Hispanic minorities have a lower incidence of AF when compared to non-Hispanic whites, referred to as the "racial paradox." Lower SES among Hispanics and African Americans may help to explain the lower incidence rates of AF compared to non-Hispanic whites. An electrocardiogram/electronic medical records database in New York State was interrogated for individuals free of AF for development of subsequent AF from 2000 to 2013. SES was assessed per zip code via a composite of 6 measures Z-scored to the New York State average. SES was reclassified into decile groups. Cox regression analysis controlling for all baseline differences was used to estimate the independent predictive ability of SES for AF. We identified 48 631 persons (43% Hispanic, 37% African Americans, and 20% non-Hispanic white; mean age 59 years; mean follow-up of 3.2 years) of which 4556 AF cases occurred. Hispanics and African Americans had lower AF risk than whites in all SES deciles (P < 0.001 by log-rank test). Higher SES was borderline associated with lower AF risk (hazard ratio: 0.990, 95% confidence interval: 0.980-1.001, P = 0.061). P trend analysis was not significant by any race/ethnic group by SES deciles for AF. Our study suggests that non-Hispanic whites were at higher risk for AF compared to nonwhites, and this was independent of SES. © 2017 Wiley Periodicals, Inc.

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-β1.

PubMed

Polejaeva, Irina A; Ranjan, Ravi; Davies, Christopher J; Regouski, Misha; Hall, Justin; Olsen, Aaron L; Meng, Qinggang; Rutigliano, Heloisa M; Dosdall, Derek J; Angel, Nathan A; Sachse, Frank B; Seidel, Thomas; Thomas, Aaron J; Stott, Rusty; Panter, Kip E; Lee, Pamela M; Van Wettere, Arnaud J; Stevens, John R; Wang, Zhongde; MacLeod, Rob S; Marrouche, Nassir F; White, Kenneth L

2016-10-01

Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF. Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12 months of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas none of 6 controls displayed sustained AF (P < 0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687 ± 212.02 seconds vs. 2.50 ± 0.88 seconds, P < 0.0001), but no persistent or permanent AF was observed. A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility. © 2016 Wiley Periodicals, Inc.

Atrial fibrillation is associated with the fibrotic remodelling of adipose tissue in the subepicardium of human and sheep atria.

PubMed

Haemers, Peter; Hamdi, Hadhami; Guedj, Kevin; Suffee, Nadine; Farahmand, Patrick; Popovic, Natasa; Claus, Piet; LePrince, Pascal; Nicoletti, Antonino; Jalife, Jose; Wolke, Carmen; Lendeckel, Uwe; Jaïs, Pierre; Willems, Rik; Hatem, Stéphane N

2017-01-01

Accumulation of atrial adipose tissue is associated with atrial fibrillation (AF). However, the underlying mechanisms remain poorly understood. We examined the relationship between the characteristics of fatty infiltrates of the atrial myocardium and the history of AF. Atrial samples, collected in 92 patients during cardiac surgery and in a sheep model of persistent AF, were subjected to a detailed histological analysis. In sections of human right atrial samples, subepicardial fatty infiltrations were commonly observed in the majority of patients. A clear difference in the appearance and fibrotic content of these fatty infiltrations was observed. Fibro-fatty infiltrates predominated in patients with permanent AF (no AF: 37 ± 24% vs. paroxysmal AF: 50 ± 21% vs. permanent AF: 64 ± 23%, P < 0.001). An inverse correlation between fibrotic remodelling and the amount of subepicardial adipose tissue suggested the progressive fibrosis of fatty infiltrates with permanent AF. This hypothesis was tested in a sheep model of AF. In AF sheep, an increased accumulation of peri-atrial fat depot was observed on cardiac magnetic resonance imaging and dense fibro-fatty infiltrations predominated in the left atria of AF sheep. Cellular inflammation, mainly consisting of functional cytotoxic T lymphocytes, was observed together with adipocyte cell death in human atria. Atrial fibrillation is associated with the fibrosis of subepicardial fatty infiltrates, a process in which cytotoxic lymphocytes might be involved. This remodelling of the atrial subepicardium could contribute to structural remodelling forming a substrate for AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Loss of atrial contractility is primary cause of atrial dilatation during first days of atrial fibrillation.

PubMed

Schotten, Ulrich; de Haan, Sunniva; Neuberger, Hans-Ruprecht; Eijsbouts, Sabine; Blaauw, Yuri; Tieleman, Robert; Allessie, Maurits

2004-11-01

Atrial fibrillation (AF) induces a progressive dilatation of the atria which in turn might promote the arrhythmia. The mechanism of atrial dilatation during AF is not known. To test the hypothesis that loss of atrial contractile function is a primary cause of atrial dilatation during the first days of AF, eight goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. AF was induced with the use of repetitive burst pacing. Atrial contractility was assessed during sinus rhythm, atrial pacing (160-, 300-, and 400-ms cycle length), and electrically induced AF. The compliance of the fibrillating right atrium was measured during unloading the atria with diuretics and loading with 1 liter of saline. All measurements were repeated after 6, 12, and 24 h of AF and then once a day during the first 5 days of AF. Recovery of the observed changes after spontaneous cardioversion was also studied. After 5 days of AF, atrial contractility during sinus rhythm or slow atrial pacing was greatly reduced. During rapid pacing (160 ms) or AF, the amplitude of the atrial pressure waves had declined to 20% of control. The compliance of the fibrillating atria increased twofold, whereas the right atrial pressure was unchanged. As a result, the mean right atrial diameter increased by approximately 12%. All changes were reversible within 3 days of sinus rhythm. We conclude that atrial dilatation during the first days of AF is due to an increase in atrial compliance caused by loss of atrial contractility during AF. Atrial compliance and size are restored when atrial contractility recovers after cardioversion of AF.

Examining rare and low-frequency genetic variants previously associated with lone or familial forms of atrial fibrillation in an electronic medical record system: a cautionary note.

PubMed

Weeke, Peter; Denny, Joshua C; Basterache, Lisa; Shaffer, Christian; Bowton, Erica; Ingram, Christie; Darbar, Dawood; Roden, Dan M

2015-02-01

Studies in individuals or small kindreds have implicated rare variants in 25 different genes in lone and familial atrial fibrillation (AF) using linkage and segregation analysis, functional characterization, and rarity in public databases. Here, we used a cohort of 20 204 patients of European or African ancestry with electronic medical records and exome chip data to compare the frequency of AF among carriers and noncarriers of these rare variants. The exome chip included 19 of 115 rare variants, in 9 genes, previously associated with lone or familial AF. Using validated algorithms querying a combination of clinical notes, structured billing codes, ECG reports, and procedure codes, we identified 1056 AF cases (>18 years) and 19 148 non-AF controls (>50 years) with available genotype data on the Illumina HumanExome BeadChip v.1.0 in the Vanderbilt electronic medical record-linked DNA repository, BioVU. Known correlations between AF and common variants at 4q25 were replicated. None of the 19 variants previously associated with AF were over-represented among AF cases (P>0.1 for all), and the frequency of variant carriers among non-AF controls was >0.1% for 14 of 19. Repeat analyses using non-AF controls aged >60 (n=14 904), >70 (n=9670), and >80 (n=4729) years did not influence these findings. Rare variants previously implicated in lone or familial forms of AF present on the exome chip are detected at low frequencies in a general population but are not associated with AF. These findings emphasize the need for caution when ascribing variants as pathogenic or causative. © 2014 American Heart Association, Inc.

The Long and Short Term Impact of Elevated Body Mass Index on Risk of New Atrial Fibrillation in the Women’s Health Study

PubMed Central

Tedrow, Usha B; Conen, David; Ridker, Paul M; Cook, Nancy R; Koplan, Bruce A; Manson, JoAnn E; Buring, Julie E; Albert, Christine M

2010-01-01

Objectives To characterize the relationship between changes in body mass index (BMI) and incident atrial fibrillation (AF) in a large cohort of women. Background Obesity and AF are increasing public health problems. The importance of dynamic obesity-associated AF risk is uncertain, and mediators are not well characterized. Methods Cases of AF were confirmed by medical record review in 34,309 participants in the Women’s Health Study. Baseline and updated measures of BMI were obtained from periodic questionnaires. Results Over 12.9 +/− 1.9 years of follow-up, 834 AF events were confirmed. BMI was linearly associated with AF risk, with a 4.7% (95% CI 3.4, 6.1, p<0.0001) increase in risk with each kg/m2. Adjustment for inflammatory markers minimally attenuated this risk. When updated measures of BMI were utilized to estimate dynamic risk, overweight (HR 1.22 95%CI 1.02, 1.45, p=0.03) and obesity (HR 1.65 95%CI 1.36, 2.00, p<0.0001) were associated with adjusted short term elevations in AF risk. Participants becoming obese during the first 60 months had a 41% adjusted increase in risk of developing AF (p=0.02) compared to those maintaining BMI <30 kg/m2. The prevalence of overweight and obesity increased over time. The adjusted proportion of incident AF attributable to short term elevations in BMI was substantial (18.3%). Conclusions In this population of apparently healthy women, BMI was associated with short and long term elevations in AF risk, accounting for a large proportion of incident AF independent of traditional risk factors. A strategy of weight control may reduce the increasing incidence of AF. PMID:20488302

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.

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.

Inflammation as a Mediator of the Association Between Race and Atrial Fibrillation: Results from the Health, Aging, and Body Composition Study

PubMed Central

Dewland, Thomas A.; Vittinghoff, Eric; Harris, Tamara B.; Magnani, Jared W.; Liu, Yongmei; Hsu, Fang-Chi; Satterfield, Suzanne; Wassel, Christina; Marcus, Gregory M.

2015-01-01

Background Despite a lower prevalence of established atrial fibrillation (AF) risk factors, Whites exhibit substantially higher rates of this arrhythmia compared to Blacks. The mechanism underlying this observation is not known. Both inflammation and obesity are risk factors for AF, and adipose tissue is a known contributor to systemic inflammation. Objectives We sought to determine the degree to which racial differences in AF risk are explained by differences in inflammation and adiposity. Methods Baseline serum inflammatory biomarker concentrations and abdominal adiposity (assessed by computed tomography) were quantified in a subset of Black and White participants without prevalent AF in the Health, Aging, and Body Composition (Health ABC) Study. Participants were prospectively followed for the diagnosis of AF using study ECGs and Medicare claims data. Cox proportional hazards models were used to determine the adjusted relative hazard of incident AF between races before and after biomarker adjustment. Results Among 2,768 participants (43% Black), 721 developed incident AF over a median follow up of 10.9 years. White race was associated with a heightened adjusted risk of incident AF (HR 1.55, 95% CI 1.30 to 1.84, p < 0.001). Abdominal adiposity was not associated with AF when added to the adjusted model. Among the studied biomarkers, adiponectin, TNF-α, TNF-α SR I, and TNF-α SR II concentrations were each higher among Whites and independently associated with a greater risk of incident AF. Together, these inflammatory cytokines mediated 42% (95% CI 15 to 119%, p = 0.004) of the adjusted race-AF association. Conclusions Systemic inflammatory pathways significantly mediate the heightened risk of AF among Whites. The higher level of systemic inflammation and concomitant increased AF risk in Whites is not explained by racial differences in abdominal adiposity or the presence of other pro-inflammatory cardiovascular comorbidities. PMID:26501131

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.

Origin and ablation of the adenosine triphosphate induced atrial fibrillation after circumferential pulmonary vein isolation: effects on procedural success rate.

PubMed

Zhang, Jinlin; Tang, Cheng; Zhang, Yonghua; Su, X I

2014-04-01

Adenosine triphosphate (ATP) has been used to provoke dormant pulmonary vein (PV) conduction after circumferential PV isolation (CPVI). However, there have been no systematic studies examining the incidence and the mechanism of ATP-induced atrial fibrillation (AF) following CPVI in paroxysmal AF. In this study, we explore the mechanism of ATP-induced AF and assess the feasibility of eliminating this response by additional radiofrequency (RF) ablation. A total of 300 consecutive patients with paroxysmal AF underwent CPVI. After all PVs were isolated, intravenous ATP (40 mg) was administered during an intravenous isoproterenol (ISP) infusion (5 μg/min). AF was reproducibly induced by ATP in 39 patients. Non-PV foci were confirmed and located in 29 of these patients at the onset of AF, including 27 foci in the superior vena cava (SVC), 1 focus in the crista terminalis, and 1 focus near the antrum of the PV. In all these cases, ATP-induced AF was eliminated after the non-PV foci were successfully ablated. For the other 10 patients, the foci triggering AF could not be confirmed or located due to the transient effect of ATP, thus no further ablation was performed. After a mean follow-up period of 18.7 ± 6.4 (8-24) months, the success rate in the ATP-induced AF group was not significantly different compared with the conventional treatment group who did not exhibit ATP-induced AF (76.9% vs 67.3%; P = 0.25). But in the subgroup of which the ATP-induced AF could be eliminated by additional RF ablation, the success rate was significantly higher than the non-ATP inducible group (86.2% vs 67.3%; P = 0.04). A large proportion of the ATP-induced AF post CPVI were initiated by rapid firing in the SVC. Eliminating this response by additional ablation may have an influence on clinical results of paroxysmal AF ablation. © 2014 Wiley Periodicals, Inc.

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.

Macular autofluorescence in eyes with cystoid macula edema, detected with 488 nm-excitation but not with 580 nm-excitation.

PubMed

Bessho, Kenichiro; Gomi, Fumi; Harino, Seiyo; Sawa, Miki; Sayanagi, Kaori; Tsujikawa, Motokazu; Tano, Yasuo

2009-06-01

Fundus autofluorescence (AF) derives from lipofuscin in the retinal pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of photoreceptors by RPE, AF imaging is expected to describe some functional aspect of the retina. In this study we report distribution of AF in patients showing macular edema. Three eyes with diabetic macular edema (DME) and 11 with retinal vein occlusion (RVO), associated with macular edema (ME) were examined. ME was determined by standard fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT). AF was recorded using a Heidelberg confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm-AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF images were analyzed by superimposing all images. All subjects presented cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488 nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal edemas did not show autofluorescence corresponding to the leakage in FA. In eyes with CME, analogous hyperautofluorescence to the CME was always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF. Moreover, this CME hyperautofluorescence was only seen in the macular area. We hypothesize that autofluorescence from CME may be considered as a "pseudo" or "relative" autofluorescence, due to macular stretching following CME that may result in lateral displacement of macular pigments (MPs) and subsequent reduction of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although this phenomenon may not directly indicate change of RPE function, it may be used as a method to assess or track CME non-invasively.

Wholly Patient-tailored Ablation of Atrial Fibrillation Guided by Spatio-Temporal Dispersion of Electrograms in the Absence of Pulmonary Veins Isolation

PubMed Central

Seitz, Julien; Bars, Clément; Théodore, Guillaume; Beurtheret, Sylvain; Lellouche, Nicolas; Bremondy, Michel; Ferracci, Ange; Faure, Jacques; Penaranda, Guillaume; Yamazaki, Masatoshi; Avula, Uma Mahesh R.; Curel, Laurence; Siame, Sabrina; Berenfeld, Omer; Pisapia, André; Kalifa, Jérôme

2017-01-01

Background The use of intra-cardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. We evaluated an electrogram marker of AF drivers: the clustering of electrograms exhibiting spatio-temporal dispersion — regardless of whether such electrograms were fractionated or not. Objective To evaluate the usefulness of spatio-temporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. Methods We prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. We tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatio-temporal dispersion of AF electrograms, we conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. Results Ablation at dispersion areas terminated AF in 95%. After ablation of 17±10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4±0.5 procedure/patient vs 41% in the validation set after 1.5±0.5 procedure/patient (arrhythmia free-survival rates: 85% vs 59%, log rank P<0.001). In comparison with the validation set, radiofrequency times (49 ± 21 minutes vs 85 ± 34.5 minutes, p=0.001) and procedure times (168 ± 42 minutes vs. 230 ± 67 minutes, p<.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver. Conclusions The clustering of intra-cardiac electrograms exhibiting spatio-temporal dispersion is indicative of AF drivers. Their ablation allows for a non-extensive and patient-tailored approach to AF ablation. Clinical trial.gov number: NCT02093949 PMID:28104073

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.

Baseline Demographics, Safety, and Patient Acceptance of an Insertable Cardiac Monitor for Atrial Fibrillation Screening: The REVEAL-AF Study.

PubMed

Conti, Sergio; Reiffel, James A; Gersh, Bernard J; Kowey, Peter R; Wachter, Rolf; Halperin, Jonathan L; Kaplon, Rachelle E; Pouliot, Erika; Verma, Atul

2017-01-01

Given the high prevalence and risk of stroke associated with atrial fibrillation (AF), detection strategies have important public health implications. The ongoing prospective, single-arm, open-label, multicenter REVEAL AF trial is evaluating the incidence of previously undetected AF using an insertable cardiac monitor (ICM) in patients without prior AF or device implantation, but who could be at risk for AF due to their demographic characteristics, +/- non-specific but compatible symptoms. Enrollment required an elevated AF risk profile defined as CHADS2≥3 or CHADS 2 =2 plus one or more of the following: coronary artery disease, renal impairment, sleep apnea or chronic obstructive pulmonary disease. Exclusions included stroke or transient ischemic attack occurring in the previous year. Of 450 subjects screened, 399 underwent a device insertion attempt, and 395 were included in the final analysis (Reveal XT: n=122; Reveal LINQ: n=273; excluded: n=4). Participants were primarily identified by demographic characteristics and the presence of nonspecific symptoms, but without prior documentation of "overt" AF. The most common symptoms were palpitations (51%), dizziness/lightheadedness/pre-syncope (36%), and shortness of breath (36%). Over 100 subjects were enrolled in each pre-defined CHADS2 subgroup (2, 3 and ≥4). AF risk factors not included in the CHADS2 score were well represented (prevalence≥15%). Procedure and/or device related serious adverse events were low, with the miniaturized Reveal LINQ ICM having a more favorable safety profile than the predicate Reveal XT (all: n=13 [3.3%]; LINQ: n=6 [2.2%]; XT: n=7 [5.7%]). These data demonstrate that REVEAL AF was successful in enrolling its target population, high risk patients were willing to undergo ICM monitoring for AF screening, and ICM use in this group is becoming increasingly safe with advancements in technology. A clinically meaningful incidence of device detected AF in this study will inform clinical decisions regarding ICM use for AF screening in patients at risk.

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.

Plasma Heating inside ICMEs by Alfvenic Fluctuations Dissipation

NASA Astrophysics Data System (ADS)

Li, H.; Wang, C.; He, J.; Zhang, L.; Richardson, J. D.; Belcher, J. W.; Tu, C.

2017-12-01

Nonlinear cascade of low-frequency Alfvenic fluctuations (AFs) is regarded as one of the candidate energy sources that heat plasma during the non-adiabatic expansion of interplanetary coronal mass ejections (ICMEs). However, AFs inside ICMEs were seldom reported in the literature. In this study, we investigate AFs inside ICMEs using observations from Voyager 2 between 1 and 6 au. It has been found that AFs with a high degree of Alfvenicity frequently occurred inside ICMEs for almost all of the identified ICMEs (30 out of 33 ICMEs) and for 12.6% of the ICME time interval. As ICMEs expand and move outward, the percentage of AF duration decays linearly in general. The occurrence rate of AFs inside ICMEs is much less than that in ambient solar wind, especially within 4.75 au. AFs inside ICMEs are more frequently presented in the center and at the boundaries of ICMEs. In addition, the proton temperature inside ICME has a similar "W"-shaped distribution. These findings suggest significant contribution of AFs on local plasma heating inside ICMEs.

Effects of Mn and Al on the Intragranular Acicular Ferrite Formation in Rare Earth Treated C-Mn Steel

NASA Astrophysics Data System (ADS)

Song, Mingming; Song, Bo; Yang, Zhanbing; Zhang, Shenghua; Hu, Chunlin

2017-07-01

The influence of Al, Mn and rare earth (RE) on microstructure of C-Mn steel was investigated. The capacities of different RE inclusions to induce intragranular acicular ferrite (AF) formation were compared. Result shows that RE treatment could make C-Mn steel from large amounts of intragranular AF. Al killed is detrimental to the formation of intragranular AF in RE-treated C-Mn steel. An upper bainite structure would replace the AF when Al content increased to 0.027 mass %. The optimal Mn content to form AF is about 0.75-1.31 mass %. The effective RE inclusion which could induce AF nucleation is La2O2S. When patches of MnS are attached on the surface of La2O2S inclusion, AF nucleation capacity of RE-containing inclusion could enlarge obviously. The existence of manganese-depleted zone and low lattice misfit would be the main reason of La-containing inclusion inducing AF nucleation in C-Mn steel.

Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

PubMed Central

Kirchhof, Paulus; Lip, Gregory Y.H.; Van Gelder, Isabelle C.; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G.; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W.; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A. John

2012-01-01

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

Presence and transcriptional activity of anaerobic fungi in agricultural biogas plants.

PubMed

Dollhofer, Veronika; Callaghan, Tony M; Griffith, Gareth W; Lebuhn, Michael; Bauer, Johann

2017-07-01

Bioaugmentation with anaerobic fungi (AF) is promising for improved biogas generation from lignocelluloses-rich substrates. However, before implementing AF into biogas processes it is necessary to investigate their natural occurrence, community structure and transcriptional activity in agricultural biogas plants. Thus, AF were detected with three specific PCR based methods: (i) Copies of their 18S genes were found in 7 of 10 biogas plants. (ii) Transcripts of a GH5 endoglucanase gene were present at low level in two digesters, indicating transcriptional cellulolytic activity of AF. (iii) Phylogeny of the AF-community was inferred with the 28S gene. A new Piromyces species was isolated from a PCR-positive digester. Evidence for AF was only found in biogas plants operated with high proportions of animal feces. Thus, AF were most likely transferred into digesters with animal derived substrates. Additionally, high process temperatures in combination with long retention times seemed to impede AF survival and activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Stressors and Coping Strategies of Older Adults With Persistent Atrial Fibrillation Prior to and Following Direct Current Cardioversion.

PubMed

Rush, Kathy L; Hatt, Linda; Shay, Matt; Gorman, Nicole; Laberge, Carol G; Reid, R Colin; Wilson, Ryan

2017-09-01

The purpose of this study was to explore the stressors and coping strategies of older adults with persistent atrial fibrillation (AF) before and after direct current cardioversion. The study used a qualitative descriptive design. Sixteen patients were recruited through an AF clinic to participate in individual interviews prior to the cardioversion and at 6 and 12 weeks post procedure. Pre-cardioversion, older adults experienced symptom and health care-related stressors superimposed on existing non-AF stressors. They used a range of emotion and problem-focused coping. Non-AF stressors increased post procedure at the same time that participants perceived less need for coping strategies with a return to regular rhythm. There was a shift from AF to non-AF related stressors following the cardioversion but a decrease in coping strategies. Older adults with AF should be encouraged to maintain use of coping strategies to manage ongoing stress and reduce the risk of AF recurrence.

Associations of Lipoprotein(a) Levels With Incident Atrial Fibrillation and Ischemic Stroke: The ARIC (Atherosclerosis Risk in Communities) Study.

PubMed

Aronis, Konstantinos N; Zhao, Di; Hoogeveen, Ron C; Alonso, Alvaro; Ballantyne, Christie M; Guallar, Eliseo; Jones, Steven R; Martin, Seth S; Nazarian, Saman; Steffen, Brian T; Virani, Salim S; Michos, Erin D

2017-12-15

Lipoprotein(a) (Lp[a]) is proatherosclerotic and prothrombotic, causally related to coronary disease, and associated with other cardiovascular diseases. The association of Lp(a) with incident atrial fibrillation (AF) and with ischemic stroke among individuals with AF remains to be elucidated. In the community-based ARIC (Atherosclerosis Risk in Communities) study cohort, Lp(a) levels were measured by a Denka Seiken assay at visit 4 (1996-1998). We used multivariable-adjusted Cox models to compare AF and ischemic stroke risk across Lp(a) levels. First, we evaluated incident AF in 9908 participants free of AF at baseline. AF was ascertained by electrocardiography at study visits, hospital International Statistical Classification of Diseases, 9th Revision ( ICD-9 ) codes, and death certificates. We then evaluated incident ischemic stroke in 10 127 participants free of stroke at baseline. Stroke was identified by annual phone calls, hospital ICD-9 Revision codes, and death certificates. The baseline age was 62.7±5.6 years. Median Lp(a) levels were 13.3 mg/dL (interquartile range, 5.2-39.7 mg/dL). Median follow-up was 13.9 and 15.8 years for AF and stroke, respectively. Lp(a) was not associated with incident AF (hazard ratio, 0.98; 95% confidence interval, 0.82-1.17), comparing those with Lp(a) ≥50 with those with Lp(a) <10 mg/dL. High Lp(a) was associated with a 42% relative increase in stroke risk among participants without AF (hazard ratio, 1.42; 95% confidence interval, 1.07-1.90) but not in those with AF (hazard ratio, 1.06; 95% confidence interval, 0.70-1.61 [ P interaction for AF=0.25]). There were no interactions by race or sex. No association was found for cardioembolic stroke subtype. High Lp(a) levels were not associated with incident AF. Lp(a) levels were associated with increased ischemic stroke risk, primarily among individuals without AF but not in those with AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Study protocol for Smartphone Monitoring for Atrial fibrillation in Real-Time in India (SMART-India): a community-based screening and referral programme.

PubMed

Soni, Apurv; Karna, Sunil; Patel, Harshil; Fahey, Nisha; Raithatha, Shyamsundar; Handorf, Anna; Bostrom, John; Bashar, Syed; Talati, Kandarp; Shah, Ravi; Goldberg, Robert J; Thanvi, Sunil; Phatak, Ajay Gajanan; Allison, Jeroan J; Chon, Ki; Nimbalkar, Somashekhar Marutirao; McManus, David D

2017-12-14

Atrial fibrillation (AF), the world's most common arrhythmia, often goes undetected and untreated in low-resource communities, including India, where AF epidemiology is undefined. AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF. This study aims to describe the epidemiology of AF in Anand District, Gujarat, India, characterise the clinical profile of individuals who are diagnosed with AF and determine the performance of two mobile technologies for community-based AF screening. This observational study builds on findings from a previous feasibility study and leverages two novel technologies as well as an existing community health programme to perform door-to-door AF screening for 2000 people from 60 villages of Anand District, Gujarat, India using local health workers. A single-lead ECG and a pulse-based application is used to screen each individual for AF three times over a period of 5 days. Participants with suspected arrhythmias are followed up by study cardiologist who makes final diagnoses. Participants diagnosed with AF are initiated on treatment based on current anticoagulation guidelines and clinical reasoning. Age-stratified and sex-stratified prevalence of AF in the Anand District will be calculated for sample and estimated for Anand distribution using survey design weights. Sociodemographic and clinical factors associated with AF will be evaluated using multivariable regression methods. Performance of each mobile technology in detecting AF will be evaluated using a 12-lead ECG interpretation as the gold standard. This protocol was approved separately by the Institutional Review Board of University of Massachusetts Medical School and the Human Research Ethics Committee at Charutar Arogya Mandal. The findings of this study will be disseminated through peer-reviewed journals and scientific conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Oxidized CaMKII Triggers Atrial Fibrillation

PubMed Central

Purohit, Anil; Rokita, Adam G.; Guan, Xiaoqun; Chen, Biyi; Koval, Olha M.; Voigt, Niels; Neef, Stefan; Sowa, Thomas; Gao, Zhan; Luczak, Elizabeth D.; Stefansdottir, Hrafnhildur; Behunin, Andrew C.; Li, Na; El-Accaoui, Ramzi N.; Yang, Baoli; Swaminathan, Paari Dominic; Weiss, Robert M.; Wehrens, Xander H.T.; Song, Long-Sheng; Dobrev, Dobromir; Maier, Lars S.; Anderson, Mark E.

2013-01-01

Background Atrial fibrillation is a growing public health problem without adequate therapies. Angiotensin II (Ang II) and reactive oxygen species (ROS) are validated risk factors for atrial fibrillation (AF) in patients, but the molecular pathway(s) connecting ROS and AF is unknown. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a ROS activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ(ox-CaMKII) could contribute to AF. Methods and Results We found ox-CaMKII was increased in atria from AF patients compared to patients in sinus rhythm and from mice infused with Ang II compared with saline. Ang II treated mice had increased susceptibility to AF compared to saline treated WT mice, establishing Ang II as a risk factor for AF in mice. Knock in mice lacking critical oxidation sites in CaMKIIδ (MM-VV) and mice with myocardial-restricted transgenic over-expression of methionine sulfoxide reductase A (MsrA TG), an enzyme that reduces ox-CaMKII, were resistant to AF induction after Ang II infusion. Conclusions Our studies suggest that CaMKII is a molecular signal that couples increased ROS with AF and that therapeutic strategies to decrease ox-CaMKII may prevent or reduce AF. PMID:24030498

Origin and Evolution of the Sponge Aggregation Factor Gene Family

PubMed Central

Grice, Laura F.; Gauthier, Marie E.A.; Roper, Kathrein E.; Fernàndez-Busquets, Xavier; Degnan, Sandie M.

2017-01-01

Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here, we characterize the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic. Further AF variance appears to be generated through individualistic patterns of RNA editing. The AF gene family varies between poriferans, with protein sequences and domains diagnostic of the AF family being present in Amphimedon and other demosponges, but absent from other sponge classes. Within the demosponges, AFs vary widely with no two species having the same AF repertoire or domain organization. The evolution of AFs suggests that their diversification occurs via high allelism, and the continual and rapid gain, loss and shuffling of domains over evolutionary time. Given the marked differences in metazoan allorecognition genes, we propose the rapid evolution of AFs in sponges provides a model for understanding the extensive diversification of self–nonself recognition systems in the animal kingdom. PMID:28104746

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 and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). Conclusions TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF. Trial registration Trial registration number: NCT00376272 PMID:23586654

Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents.

PubMed

Wu, J; Liu, P; Zhu, J L; Maddukuri, S; Zern, M A

1998-03-01

To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73%+/-3.9%) was markedly higher (P < .005) than CL (16.5%+/-1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14C-AF-L, and was much higher than in 14C-CL-injected mice (1.5-fold). In vitro incubation of isolated rat hepatocytes with 14C-AF-L or intravenous injection of 14C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14C-CL (P < .01-.005). AF-L-associated 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl4-treated mice (196+/-79 vs. 2,107+/-235 U/mL; P < .01). The ALT level in CCl4 + VE-AF-L group was decreased to 38+/-16 units/mL, which was significantly lower than the CC14 + VE-CL group (P < .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the protective effect of VE liposomes on CC14-induced acute liver injury in mice. Preferential hepatocyte incorporation of AF-L liposomes suggests a useful hepatocyte-targeting approach for drug delivery and gene transfection.

Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity

PubMed Central

Linnemann, Amelia K.; Krawetz, Stephen A.

2009-01-01

DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14–18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment. PMID:19276204

DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier.

PubMed

Santos, Margarida A; Faryabi, Robert B; Ergen, Aysegul V; Day, Amanda M; Malhowski, Amy; Canela, Andres; Onozawa, Masahiro; Lee, Ji-Eun; Callen, Elsa; Gutierrez-Martinez, Paula; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Deshpande, Aniruddha; Sharrow, Susan; Rossi, Derrick J; Ito, Keisuke; Ge, Kai; Aplan, Peter D; Armstrong, Scott A; Nussenzweig, André

2014-10-02

Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4(-/-) MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.

Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

DTIC Science & Technology

2012-10-01

DAPS AF constructs, fabricated complete DAPS comprised of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and designed and commencement of...of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and design and commencement of construction of a novel multi-axis bioreactor that will be... nanofiber AF and a hyaluronic acid hydrogel NP We have commenced fabrication and in vitro pre-culture of composite DAPS constructs. An AF region

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.

Aerobic Fitness and Body Mass Index in Individuals with Schizophrenia: Implications for Neurocognition and Daily Functioning

PubMed Central

Kimhy, David; Vakhrusheva, Julia; Bartels, Matthew N.; Armstrong, Hilary F.; Ballon, Jacob S.; Khan, Samira; Chang, Rachel W.; Hansen, Marie C.; Ayanruoh, Lindsey; Smith, Edward E.; Sloan, Richard P.

2014-01-01

Previous reports indicate that among healthy individuals low Aerobic Fitness (AF) and high Body-Mass Index (BMI) predict poor neurocognition and daily-functioning. It is unknown whether these associations extend to disorders characterized by poor neurocognition, such as schizophrenia. Therefore, we compared AF and BMI in individuals with schizophrenia and non-clinical controls, and then within the schizophrenia group we examined the links between AF, BMI, neurocognition and daily-functioning. Thirty-two individuals with schizophrenia and 64 gender- and age-matched controls completed assessments of AF (indexed by VO2max) and BMI. The former also completed measures of neurocognition, daily-functioning and physical activity. The schizophrenia group displayed significantly lower AF and higher BMI. In the schizophrenia group, AF was significantly correlated with overall neurocognition (r=0.57), along with executive functioning, working memory, social cognition, and processing speed. A hierarchical regression analysis indicated that AF accounted for 22% of the neurocognition variance. Furthermore, AF was significantly correlated with overall daily-functioning (r=0.46). In contrast, BMI displayed significant inverse correlations with neurocognition, but no associations to daily-functioning. AF was significantly correlated physical activity. The authors discuss the potential use of AF-enhancing interventions to improve neurocognitive and daily-functioning in schizophrenia, along with putative neurobiological mechanisms underlying these links, including Brain-Derived Neurotrophic Factor. PMID:25219618

Detection of atrial fibrillation with seismocardiography.

PubMed

Pankaala, Mikko; Koivisto, Tero; Lahdenoja, Olli; Kiviniemi, Tuomas; Saraste, Antti; Vasankari, Tuija; Airaksinen, Juhani

2016-08-01

In this paper we study the feasibility of seismocardiography (SCG) for the detection of Atrial Fibrillation (AF). In this preclinical study, data acquired from one patient having paroxysmal AF (no other heart diseases) is used to introduce specific changes in SCG signal due to AF. Observed changes and phenomena create a foundation for the development of SCG-based AF detection algorithms. SCG data was recorded from the sternum of an AF patient in dorso-ventral direction while at rest in a supine position using a three-axis high precision MEMS accelerometer simultaneously with a one-lead ECG. In contrast to ECG, the magnitude of beats registered with SCG varies considerably from beat to beat during AF. We show that the magnitude of the beats is not random but is in relation to beat intervals. It is shown that extra indicators for detecting AF become available when SCG data is combined with electrocardiographical (ECG) data; there is a certain behavior in the electromechanical delay characteristic of the AF. It is discussed how all this information can be taken advantage of in the detection of AF. Today electrocardiography (ECG) is the primary method for diagnosing arrhythmias, but there is a growing need for simpler and more convenient method for detecting asymptomatic AF. Given the very small dimensions of modern MEMS accelerometers (2mm×2mm), a reliable MEMS based measurement may provide totally new venues for arrhythmia detection.

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials.

PubMed

Brown, Jennifer R; Moslehi, Javid; O'Brien, Susan; Ghia, Paolo; Hillmen, Peter; Cymbalista, Florence; Shanafelt, Tait D; Fraser, Graeme; Rule, Simon; Kipps, Thomas J; Coutre, Steven; Dilhuydy, Marie-Sarah; Cramer, Paula; Tedeschi, Alessandra; Jaeger, Ulrich; Dreyling, Martin; Byrd, John C; Howes, Angela; Todd, Michael; Vermeulen, Jessica; James, Danelle F; Clow, Fong; Styles, Lori; Valentino, Rudy; Wildgust, Mark; Mahler, Michelle; Burger, Jan A

2017-10-01

The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation ( clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021 ). Copyright© 2017 Ferrata Storti Foundation.

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials

PubMed Central

Brown, Jennifer R.; Moslehi, Javid; O’Brien, Susan; Ghia, Paolo; Hillmen, Peter; Cymbalista, Florence; Shanafelt, Tait D.; Fraser, Graeme; Rule, Simon; Kipps, Thomas J.; Coutre, Steven; Dilhuydy, Marie-Sarah; Cramer, Paula; Tedeschi, Alessandra; Jaeger, Ulrich; Dreyling, Martin; Byrd, John C.; Howes, Angela; Todd, Michael; Vermeulen, Jessica; James, Danelle F.; Clow, Fong; Styles, Lori; Valentino, Rudy; Wildgust, Mark; Mahler, Michelle; Burger, Jan A.

2017-01-01

The first-in-class Bruton’s tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6–16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation (clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021). PMID:28751558

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.

Elevated admission N-terminal pro-brain natriuretic peptide level predicts the development of atrial fibrillation in general surgical intensive care unit patients.

PubMed

Chokengarmwong, Nalin; Yeh, Daniel Dante; Chang, Yuchiao; Ortiz, Luis Alfonso; Kaafarani, Haytham M A; Fagenholz, Peter; King, David R; DeMoya, Marc; Butler, Kathryn; Lee, Jarone; Velmahos, George; Januzzi, James Louis; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent

2017-09-01

New onset atrial fibrillation (AF) in critically ill surgical patients is associated with significant morbidity and increased mortality. N-terminal pro-B type natriuretic peptide (NT-proBNP) is released by cardiomyocytes in response to stress and may predict AF development after surgery. We hypothesized that elevated NT-proBNP level at surgical intensive care unit (ICU) admission predicts AF development in a general surgical and trauma population. From July to October 2015, NT-proBNP concentrations were measured at ICU admission. Abnormal NT-proBNP concentrations were defined by age-adjusted cut-offs. We examined the relationship between the development of AF and demographics, clinical variables, and NT-proBNP level using univariate analysis and a multivariable logistic regression model. Three hundred eighty-seven subjects were included in the cohort, none of whom were in AF at ICU admission. The median age was 63 years (52-73 years), and 40.3% were women. The risk of developing AF was higher for abnormal versus normal NT-proBNP (22% vs. 4%; p < 0.0001). Using optimal derived cutoffs (regardless of age), the risk of developing AF was 2% for NT-proBNP less than 600 ng/L, 15% for NT-proBNP of 600 ng/L to 1,999 ng/L, and 27% for NT-proBNP of 2,000 ng/L or greater. Multiple logistic regression analysis identified three independent predictors for new-onset AF: age, older than 70 years (odds ratio [OR], 3.7, 95% confidence interval [CI], 1.5-9.3), history of AF (OR, 25.3; 95% CI, 9.6-67.0), and NT-proBNP of 600 or greater (OR, 4.3; 95% CI, 1.3-14.2). When none or only one predictor was present, AF incidence was less than 1%. When all three predictors were present, AF incidence was 66%. For subjects 70 years or older but no history of AF, AF incidence was 12.8% when NT-proBNP was 600 or greater compared with 0% when NT-proBNP was less than 600. For subjects younger than 70 years with a history of AF, AF incidence was 44.4% when NT-proBNP was 600 or higher compared to 0% when NT-proBNP was less than 600. Elevated NT-proBNP at ICU admission in general surgical and trauma patients is predictive of AF development in the first 3 ICU days. Addition of NT-proBNP measurement to known risk factors can improve predictive power and identify patients who might potentially benefit from evidence-based prophylactic treatment for AF.

Fundus Autofluorescence and Photoreceptor Cell Rosettes in Mouse Models

PubMed Central

Flynn, Erin; Ueda, Keiko; Auran, Emily; Sullivan, Jack M.; Sparrow, Janet R.

2014-01-01

Purpose. This study was conducted to study correlations among fundus autofluorescence (AF), RPE lipofuscin accumulation, and photoreceptor cell degeneration and to investigate the structural basis of fundus AF spots. Methods. Fundus AF images (55° lens; 488-nm excitation) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired in pigmented Rdh8−/−/Abca4−/− mice (ages 1–9 months) with a confocal scanning laser ophthalmoscope (cSLO). For quantitative fundus AF (qAF), gray levels (GLs) were calibrated to an internal fluorescence reference. Retinal bisretinoids were measured by quantitative HPLC. Histometric analysis of outer nuclear layer (ONL) thicknesses was performed, and cryostat sections of retina were examined by fluorescence microscopy. Results. Quantified A2E and qAF intensities increased until age 4 months in the Rdh8−/−/Abca4−/− mice. The A2E levels declined after 4 months of age, but qAF intensity values continued to rise. The decline in A2E levels in the Rdh8−/−/Abca4−/− mice paralleled reduced photoreceptor cell viability as reflected in ONL thinning. Hyperautofluorescent puncta in fundus AF images corresponded to photoreceptor cell rosettes in SD-OCT images and histological sections stained with hematoxylin and eosin. The inner segment/outer segment–containing core of the rosette emitted an autofluorescence detected by fluorescence microscopy. Conclusions. When neural retina is disordered, AF from photoreceptor cells can contribute to noninvasive fundus AF images. Hyperautofluorescent puncta in fundus AF images are attributable, in at least some cases, to photoreceptor cell rosettes. PMID:25015357

Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation.

PubMed

Navara, Rachita; Leef, George; Shenasa, Fatemah; Kowalewski, Christopher; Rogers, Albert J; Meckler, Gabriela; Zaman, Junaid A B; Baykaner, Tina; Park, Shirley; Turakhia, Mintu P; Zei, Paul; Viswanathan, Mohan; Wang, Paul J; Narayan, Sanjiv M

2018-01-29

To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI). It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods. We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity. In 22 patients (age 60.1 ± 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n  =  20) and focal (n  =  2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P < 0.001) with similar stability (P < 0.001). Vagal slowing was not observed at sites of AF termination. PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF. © 2018 Wiley Periodicals, Inc.

Estimating the Prevalence of Atrial Fibrillation from A Three-Class Mixture Model for Repeated Diagnoses

PubMed Central

Li, Liang; Mao, Huzhang; Ishwaran, Hemant; Rajeswaran, Jeevanantham; Ehrlinger, John; Blackstone, Eugene H.

2016-01-01

Atrial fibrillation (AF) is an abnormal heart rhythm characterized by rapid and irregular heart beat, with or without perceivable symptoms. In clinical practice, the electrocardiogram (ECG) is often used for diagnosis of AF. Since the AF often arrives as recurrent episodes of varying frequency and duration and only the episodes that occur at the time of ECG can be detected, the AF is often underdiagnosed when a limited number of repeated ECGs are used. In studies evaluating the efficacy of AF ablation surgery, each patient undergo multiple ECGs and the AF status at the time of ECG is recorded. The objective of this paper is to estimate the marginal proportions of patients with or without AF in a population, which are important measures of the efficacy of the treatment. The underdiagnosis problem is addressed by a three-class mixture regression model in which a patient’s probability of having no AF, paroxysmal AF, and permanent AF is modeled by auxiliary baseline covariates in a nested logistic regression. A binomial regression model is specified conditional on a subject being in the paroxysmal AF group. The model parameters are estimated by the EM algorithm. These parameters are themselves nuisance parameters for the purpose of this research, but the estimators of the marginal proportions of interest can be expressed as functions of the data and these nuisance parameters and their variances can be estimated by the sandwich method. We examine the performance of the proposed methodology in simulations and two real data applications. PMID:27983754

Lone atrial fibrillation: what is known and what is to come.

PubMed

Potpara, T S; Lip, G Y H

2011-04-01

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adults, affecting >1% of general population. Atrial fibrillation is commonly associated with structural heart disease and is a major cause of significant cardiovascular morbidity and mortality. AF sometimes develops in a subset of young patients (e.g. aged ≤60 years), with no evidence of associated cardiopulmonary or other comorbid disease (including hypertension), and has been referred to as 'lone AF'. The latter generally has a favourable prognosis; the prognostic and therapeutic implications of an accurate identification of patients with truly lone AF (that is, truly at low risk of complications), if any, would be of the utmost importance. The true prevalence of lone AF is unknown, varying between 1.6% and 30%, depending on the particular study population. Nonetheless, novel risk factors for AF, including obesity, metabolic syndrome, sleep apnea, alcohol consumption, endurance sports, anger, hostility, subclinical atherosclerosis and others, have been increasingly recognised. Also, various underlying pathophysiological mechanisms predisposing to AF, including increased atrial stretch, structural and electrophysiological alterations, autonomic imbalance, systemic inflammation, oxidative stress and genetic predisposition, have been proposed. The growing evidence of these diverse (and numerous) pathogenic mechanisms and factors related to AF inevitably raises the question of whether 'lone AF' does exist at all. In this review article, we summarise the current knowledge of the epidemiology, pathophysiology, clinical course and treatment of patients with so-called 'lone AF' and outline emerging insights into its pathogenesis and the potential therapeutic implications of a diagnosis of lone AF. © 2011 Blackwell Publishing Ltd.

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.

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

Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian agenda.

PubMed

Chen, Chen-Huan; Chen, Mien-Cheng; Gibbs, Harry; Kwon, Sun U; Lo, Sidney; On, Young Keun; Rosman, Azhari; Suwanwela, Nijasri C; Tan, Ru San; Tirador, Louie S; Zirlik, Andreas

2015-07-15

Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Total and interatrial epicardial adipose tissues are independently associated with left atrial remodeling in patients with atrial fibrillation.

PubMed

Shin, Seung Yong; Yong, Hwan Seok; Lim, Hong Euy; Na, Jin Oh; Choi, Cheol Ung; Choi, Jong Il; Kim, Seong Hwan; Kim, Jin Won; Kim, Eung Ju; Park, Sang Weon; Rha, Seung-Woon; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo; Kim, Young-Hoon

2011-06-01

As epicardial adipose tissue (EAT) is a metabolically active visceral fat, potential interaction between EAT and myocardium is strongly suggested. The aims of this study were to determine whether the amount and regional distribution of EAT are related to the chronicity of atrial fibrillation (AF) and left atrial (LA) remodeling. This study consisted of 40 subjects with paroxysmal AF (PAF) and 40 with persistent AF (PeAF). Eighty subjects with no history of AF were enrolled as controls. Total volume of EAT (EAT(total)), regional thickness of EAT, and LA volume (LAV) were measured by multislice computed tomography. In the AF group, blood samples were drawn from coronary sinus for analysis of inflammatory cytokines including adiponectin. Compared with controls, AF subjects had larger LAV, EAT(total), and the thicknesses of periatrial EAT including interatrial septum (IAS). However, the thicknesses of periventricular EAT were not different between the groups. The PeAF subjects had larger LAV, EAT(total), and periatrial EAT thicknesses, higher levels of inflammatory cytokines, and lower level of adiponectin than did the PAF subjects. Adiponection level was significantly associated with EAT(total) and IAS thickness. Multivariate analysis revealed that EAT(total) (P = 0.004) and IAS thickness (P = 0.016) were independently associated with LAV. EAT(total) and thickness of periatrial EAT were significantly larger in AF subjects compared to those of the matched controls and were closely related to the chronicity of AF. Moreover, EAT(total) and IAS thickness were independently associated with LAV in subjects with AF. © 2011 Wiley Periodicals, Inc.

Estimating the prevalence of atrial fibrillation from a three-class mixture model for repeated diagnoses.

PubMed

Li, Liang; Mao, Huzhang; Ishwaran, Hemant; Rajeswaran, Jeevanantham; Ehrlinger, John; Blackstone, Eugene H

2017-03-01

Atrial fibrillation (AF) is an abnormal heart rhythm characterized by rapid and irregular heartbeat, with or without perceivable symptoms. In clinical practice, the electrocardiogram (ECG) is often used for diagnosis of AF. Since the AF often arrives as recurrent episodes of varying frequency and duration and only the episodes that occur at the time of ECG can be detected, the AF is often underdiagnosed when a limited number of repeated ECGs are used. In studies evaluating the efficacy of AF ablation surgery, each patient undergoes multiple ECGs and the AF status at the time of ECG is recorded. The objective of this paper is to estimate the marginal proportions of patients with or without AF in a population, which are important measures of the efficacy of the treatment. The underdiagnosis problem is addressed by a three-class mixture regression model in which a patient's probability of having no AF, paroxysmal AF, and permanent AF is modeled by auxiliary baseline covariates in a nested logistic regression. A binomial regression model is specified conditional on a subject being in the paroxysmal AF group. The model parameters are estimated by the Expectation-Maximization (EM) algorithm. These parameters are themselves nuisance parameters for the purpose of this research, but the estimators of the marginal proportions of interest can be expressed as functions of the data and these nuisance parameters and their variances can be estimated by the sandwich method. We examine the performance of the proposed methodology in simulations and two real data applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catabolic Effects of Endothelial Cell-Derived Microparticles on Disc Cells: Implications in Intervertebral Disc Neovascularization and Degeneration

PubMed Central

Pohl, Pedro H. I.; Lozito, Thomas P.; Cuperman, Thais; Yurube, Takashi; Moon, Hong J.; Ngo, Kevin; Tuan, Rocky S.; Croix, Claudette St.; Sowa, Gwendolyn A.; Rodrigues, Luciano M. R.; Kang, James D.; Vo, Nam V.

2017-01-01

Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 hours with 250μg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3 fold), MMP-3 (4.5 fold) and MMP-13 (5.5 fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. PMID:27246627

Mind the model: effect of instrumentation on inducibility of atrial fibrillation in a sheep model.

PubMed

Willems, Rik; Holemans, Patricia; Ector, Hugo; Sipido, Karin R; Van de Werf, Frans; Heidbüchel, Hein

2002-01-01

Atrial electrical remodeling, shortening of the atrial effective refractory period (AERP) underlying atrial fibrillation (AF) has been described in different animal models. However, there remains some controversy regarding the time course of this electrical remodeling and the need for secondary factors in the development of AF. We investigated the effect of instrumentation on the inducibility of AF. We hypothesized that epicardial instrumentation could be a confounding factor that accelerates the development of AF. Thirty sheep were rapidly atrially paced at 600 beats/min for 15 weeks: 15 were endocardially instrumented and paced (endo), and 15 were both endocardially and epicardially instrumented. Six of these animals were endocardially paced (sham) and 9 were epicardially paced (epi). The underlying rhythm was determined at regular intervals, and electrophysiologic study was performed. AF developed significantly faster in the epi group. After 3 weeks of pacing, the cumulative incidence of sustained AF (>1 hour) already was 70% in this group versus only 14% and 20% in the endo and sham groups, respectively. After 15 weeks of pacing, this difference was no longer evident. Baseline AERP and minimal AERP, reached before the development of AF, were not significantly different in the three groups. Epicardial instrumentation (epi and sham) increased baseline left and right atrial pressures, but only epicardial stimulation (epi) led to early development of AF. In this sheep model of AF, the experimental setup is a major determinant of the inducibility of AF. Not epicardial instrumentation per se but epicardial stimulation accelerated the development of AF. Different animal models

Photoreceptor cells as a source of fundus autofluorescence in recessive Stargardt disease.

PubMed

Paavo, Maarjaliis; Lee, Winston; Allikmets, Rando; Tsang, Stephen; Sparrow, Janet R

2018-04-27

Bisretinoid fluorophores form in photoreceptor outer segments from nonenzymatic reactions of vitamin A aldehyde. The short-wavelength autofluorescence (SW-AF) of fundus flecks in recessive Stargardt disease (STGD1) suggests a connection to these fluorophores. Through multimodal imaging, we sought to elucidate this link. Flecks observed in SW-AF images often colocalized with foci exhibiting reduced or absent near-infrared autofluorescence signal, the source of which is melanin in retinal pigment epithelial (RPE) cells. With serial imaging, changes in near-infrared autofluorescence (NIR-AF) preceded the onset of fleck hyperautofluorescence in SW-AF images and fleck profiles in NIR-AF images tended to be larger. Flecks in SW-AF and NIR-AF images also corresponded to hyperreflective lesions traversing photoreceptor-attributable bands in horizontal SD-OCT scans. The hyperreflective lesions interrupted adjacent OCT reflectivity bands and were associated with thinning of the outer nuclear layer. These SD-OCT findings are attributable to photoreceptor cell degeneration. Progressive increases and decreases in the SW-AF intensity of flecks were evident in color-coded quantitative fundus autofluorescence maps. In some cases, flecks appeared to spread radially from the fovea to approximately 8° of eccentricity, beyond which a circumferential spread characterized the distribution. Since the NIR-AF signal is derived from melanin and loss of this autofluorescence is indicative of RPE atrophy, the SW-AF of flecks cannot be accounted for by bisretinoid lipofuscin in RPE. Instead, we suggest that the bisretinoid serving as the source of the SW-AF signal, resides in photoreceptors, the cell that is also the site of bisretinoid synthesis. © 2018 Wiley Periodicals, Inc.

On-Board GPS Clock Monitoring for Signal Integrity

DTIC Science & Technology

2010-11-01

to-alert requirements to permit primary reliance for safety -of-life applications. Augmentation systems are being developed and deployed to address...virtually no false alerts from the combined system . With three running, on-board AFSs , occasional breaks of the error threshold can be allowed if the... system can be assured of transfer to another AFS within a period shorter than the required TTA. With only two AFSs on board running and measured

Roadmap for the Hypersonics Programs of the Department of Defense

DTIC Science & Technology

2008-02-01

development and integration of a 1MW e-bean system to provide the necessary energy into the wind tunnel flow field to enable longer duration experiments at...acquired. Finally, “Test and Evaluation” (T&E) is defined as tests and experiments in support of research development and acquisition of systems...Research Experimentation (HIFiRE) project, the DARPA/AF Falcon program, and the DoD Next Generation Launch planning activities. 13 Joint

Nonlinear System Analysis in Bipolar Integrated Circuits.

DTIC Science & Technology

1980-01-01

H2 (fl,f 6), H2 (f2,f4), and H2 (f3,f4) are all equal, Equation (7-8) can be written as v M(t) = mA2 H2 (fl’-f 2) cos[27(f ,-f2)t] (7-9) The AF...and R. A. AMADORI: Micro- wave Interference Effect in Bipolar Transistors, IEEE Trans. EMC, Vol. EMC-17, pp. 216-219, November 1975. 55. KAPLAN , G

A Bibliography of Selected Publications: Project Air Force, 5th Edition

DTIC Science & Technology

1989-05-01

Dyna - R-3028-AF. A Dynamic Retention Model for Air Force Officers: METRIC’s DL and and Pipeilne Variability. M. J. Carrillo. Theory and Estimates. G...Theorem and Dyna - and Support. METRIC’s Demand and Pipeline Variability. R-3255-AF. Aircraft Airframe Cost Estimating Relationships: N-2283/1-AF...U). 1970-1985. N-2409-AF. Tanker Splitting Across the SlOP Bomber Force R-3389-AF. Dyna -METRIC Version 4: Modeling Worldwide (U). Logistics Support of

(BNL/DoE-hyped) ``Self-Organized-Criticality'' (SOC) is Merely Newton's(1687) Third Law of Motion F = ma REdiscovery: LONG PRE-``Bak''!!!

NASA Astrophysics Data System (ADS)

Bak, P. R. E.; Newton, I.; Siegel, Edward Carl-Ludwig

2011-03-01

"Bak"/BNL/DoE "self-organized-criticality"(SOC) usual BNL/DoE media-hype P.R spin-doctoring "show-biz" "Bush-waaa-...-aaah!!!" is manifestly-demonstrated in two distinct ways to be nothing but Newton's Third Law of Motion F = ma REdiscovery!!! PHYSICS: (1687) cross-multiplied F = ma rewritten as 1/m = a/F = OUTPUT/INPUT = EFFECT/ CAUSE = inverse-mass mechanical-susceptibility = X ("w "); X ("w ") (F.-D. theorem-equivalence /proportionality) P("w ") "noise" power-spectrum; E w ; and E (any/all media upper-limiting-speeds) m. Thus: w E m; inversion yields: 1/w 1 /E 1 /m a/F = X ("w ") P("w "); hence: F = ma dual/inverse-integral-transform is "'SOC"'s" P(w) 1 / w (1) !!! ; "PURE"-MATHS: F = ma double-integral time-series s(t) = [vot + (1/2) at (2) ] inverse/dual-integral-transform formally defines power-spectrum: P (w) = S { s (t) e [ - (iORnoi) wt ] } dt = S { [ vot + (1 / 2) at 2) ] e [ - (iORnoi) wt ] } dt = voS { te [ - (iORnoi) wt ] } dt + (1 / 2) S { [ a = / = a (t) ] e [ - (iORnoi) wt) } dt = vo (d / dw) Delta (w) + (1 / 2) [ a = / = a (t) ] (d / dw) (2) Delta (w) = vo / w (0) + (1 / 2) [ a = / = a (t) ] / w 1 : ifa = 0 , then P(w) 1 / w 0 , VS . ifa = / = a (t) = / = 0 , then P(w) 1 /w; = by physics: ``SOC'' RE-expresses F = ma!!!: ``just `a tad' late/tardy'' REdiscovery of F=ma: LONG PRE-"Bak"!!!

Atrial fibrillation in the elderly: physicians' attitudes to anticoagulation.

PubMed

King, D; Davies, K N; Slee, A; Silas, J H

1995-01-01

The use of warfarin and aspirin for the primary prevention of stroke in elderly patients with atrial fibrillation (AF) is controversial. To establish current practice we circulated a questionnaire to 300 geriatricians (G) and 300 cardiologists (C). The response rates were 47% G and 51% C. Most physicians prescribed warfarin in AF associated with mitral stenosis (G vs C, 86% vs 89%, NS). Cardiologists were more likely to prescribe warfarin in AF associated with dilated cardiomyopathy (G vs C, 52% vs 86%, P < 0.01). A minority would prescribe warfarin in aortic valve disease and AF (G vs C, 37% vs 24%, P < 0.05) and lone AF (G vs C, 10% vs 26%, P < 0.01). Aspirin was favoured in aortic valve disease and lone AF. The cardiologists were less reluctant to use warfarin in the young and more likely to electrically cardiovert the young with chronic AF.

Hypertension and atrial fibrillation: epidemiology, pathophysiology and therapeutic implications.

PubMed

Lau, Y-F; Yiu, K-H; Siu, C-W; Tse, H-F

2012-10-01

Hypertension is one of the most important risk factors associated with atrial fibrillation (AF) and increased the risk of cardiovascular events in patients with AF. However, the pathophysiological link between hypertension and AF is unclear. Nevertheless, this can be explained by the hemodynamic changes of the left atrium secondary to long standing hypertension, resulting in elevated left atrium pressure and subsequently left atrial enlargement. Moreover, the activation of renin-angiotensin-aldosterone system (RAAS) activation in patients with hypertension induces left atrial fibrosis and conduction block in the left atrium, resulting in the development of AF. Accordingly, recent studies have shown that effective blockage of RAAS by angiotensin converting enzyme inhibitors or angiotensin receptor antagonist may be effective in both primary and secondary prevention of AF in patients with hypertension, although with controversies. In addition, optimal antithrombotic therapy, blood pressure control as well as rate control for AF are key to the management of patients with AF.

Left Atrial Appendage Closure in Atrial Fibrillation: A World without Anticoagulation?

PubMed Central

Contractor, Tahmeed; Khasnis, Atul

2011-01-01

Atrial Fibrillation (AF) is a common arrhythmia with an incidence that is as high as 10% in the elderly population. Given the large proportion of strokes caused by AF as well as the associated morbidity and mortality, reducing stroke burden is the most important part of AF management. While warfarin significantly reduces the risk of AF-related stroke, perceived bleeding risks and compliance limit its widespread use in the high-risk AF population. The left atrial appendage is believed to be the “culprit” for thrombogenesis in nonvalvular AF and is a new therapeutic target for stroke prevention. The purpose of this review is to explore the evolving field of percutaneous LAA occlusion. After briefly highlighting the risk of stroke with AF, problems with warfarin, and the role of the LAA in clot formation, this article discusses the feasibility and efficacy of various devices which have been developed for percutaneous LAA occlusion. PMID:21559225

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...

78 FR 72071 - Notice of Availability: Application Requirements for the American Assured Fuel Supply

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-02

... the material in the AFS beyond ensuring that Westinghouse, the private company storing the AFS LEU for.... Policy and Process for Accessing AFS Material The DOE requests that persons or companies that seek to... or make any warranty, express or implied beyond assuring that Westinghouse, the company storing AFS...

Atrial Fibrillation in Hematologic Malignancies, Especially After Autologous Hematopoietic Stem Cell Transplantation: Review of Risk Factors, Current Management, and Future Directions.

PubMed

Mathur, Pankaj; Paydak, Hakan; Thanendrarajan, Sharmilan; van Rhee, Frits

2016-02-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality worldwide. In addition to well-established risk factors, cancer has been increasingly associated with the development of AF. Its increased occurrence in those with hematologic malignancies has been attributed to chemotherapeutic agents and autologous hematopoietic stem cell transplantation (AHSCT). Recently, a few studies have attempted to define the etiopathogenesis of AF in hematologic malignancies. The management of AF in these patients is challenging because of the concurrent complicating factors, such as thrombocytopenia, orthostatic hypotension, and cardiac amyloidosis. More studies are needed to define the management of AF, especially rate versus rhythm control and anticoagulation. Arrhythmias, in particular, AF, have been associated with an increased length of stay, increased intensive care unit admissions, and greater cardiovascular mortality. In the present review, we describe AF in patients with hematologic malignancies, the risk factors, especially after AHSCT, and the current management of AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Predicting termination of atrial fibrillation based on the structure and quantification of the recurrence plot.

PubMed

Sun, Rongrong; Wang, Yuanyuan

2008-11-01

Predicting the spontaneous termination of the atrial fibrillation (AF) leads to not only better understanding of mechanisms of the arrhythmia but also the improved treatment of the sustained AF. A novel method is proposed to characterize the AF based on structure and the quantification of the recurrence plot (RP) to predict the termination of the AF. The RP of the electrocardiogram (ECG) signal is firstly obtained and eleven features are extracted to characterize its three basic patterns. Then the sequential forward search (SFS) algorithm and Davies-Bouldin criterion are utilized to select the feature subset which can predict the AF termination effectively. Finally, the multilayer perceptron (MLP) neural network is applied to predict the AF termination. An AF database which includes one training set and two testing sets (A and B) of Holter ECG recordings is studied. Experiment results show that 97% of testing set A and 95% of testing set B are correctly classified. It demonstrates that this algorithm has the ability to predict the spontaneous termination of the AF effectively.

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.

Antiferromagnetic layer thickness dependence of noncollinear uniaxial and unidirectional anisotropies in NiFe/FeMn/CoFe trilayers

NASA Astrophysics Data System (ADS)

Choi, Hyeok-Cheol; You, Chun-Yeol; Kim, Ki-Yeon; Lee, Jeong-Soo; Shim, Je-Ho; Kim, Dong-Hyun

2010-06-01

We have investigated the dependence of magnetic anisotropies of the exchange-biased NiFe/FeMn/CoFe trilayers on the antiferromagnetic (AF) layer thickness (tAF) by measuring in-plane angular-dependent ferromagnetic resonance fields. The resonance fields of NiFe and CoFe sublayers are shifted to lower and higher values compared to those of single unbiased ferromagnetic (F) layers, respectively, due to the interfacial exchange coupling when tAF≥2nm . In-plane angular dependence of resonance field reveals that uniaxial and unidirectional anisotropies coexist in the film plane, however, they are not collinear with each other. It is found that these peculiar noncollinear anisotropies significantly depend on tAF . The angle of misalignment displays a maximum around tAF=5nm and converges to zero when tAF is thicker than 10 nm. Contributions from thickness-dependent AF anisotropy and spin frustrations at both F/AF interfaces due to the structural imperfections should be accounted in order to understand the AF-layer thickness dependence of noncollinear magnetic anisotropies.

Nurse-led clinics for atrial fibrillation: managing risk factors.

PubMed

Jacob, Liril

2017-12-14

Atrial fibrillation (AF) is the most common and sustained cardiac arrhythmia rated by cardiologists as one of the most difficult conditions to manage. Traditionally, AF management has focused on the three pillars of rate control, rhythm control and anticoagulation. However, more recently, cardiovascular risk-factor management in AF has emerged as a fourth and essential pillar, delivering improved patient outcomes. In the UK, AF is a condition that is often managed poorly, with patients reporting a lack of understanding of their condition and treatment options. Many aspects of assessment and communication in AF management are time consuming. Failure to address those aspects may negatively affect the quality of care. Nurse-led clinics can contribute significantly in the areas of patient education and sustained follow-up care, improving outcomes and addressing current deficiencies in AF risk-factor management due to scarcity of medical resources. This article discusses the major cardiovascular risk factors associated with AF, drawing on evidence from the literature, and considers the effectiveness and implications for practice of introducing community-based nurse-led clinics for risk-factor management in patients with AF.

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.

Hypertension and Atrial Fibrillation: An Intimate Association of Epidemiology, Pathophysiology, and Outcomes.

PubMed

Dzeshka, Mikhail S; Shahid, Farhan; Shantsila, Alena; Lip, Gregory Y H

2017-08-01

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia found in clinical practice. AF rarely exists as a single entity but rather as part of a diverse clinical spectrum of cardiovascular diseases, related to structural and electrical remodeling within the left atrium, leading to AF onset, perpetuation, and progression. Due to the high overall prevalence within the AF population arterial hypertension plays a significant role in the pathogenesis of AF and its complications. Fibroblast proliferation, apoptosis of cardiomyocytes, gap junction remodeling, accumulation of collagen both in atrial and ventricular myocardium all accompany ageing-related structural remodeling with impact on electrical activity. The presence of hypertension also stimulates oxidative stress, systemic inflammation, rennin-angiotensin-aldosterone and sympathetic activation, which further drives the remodeling process in AF. Importantly, both hypertension and AF independently increase the risk of cardiovascular and cerebrovascular events, e.g., stroke and myocardial infarction. Given that both AF and hypertension often present with limited on patient wellbeing, treatment may be delayed resulting in development of complications as the first clinical manifestation of the disease. Antithrombotic prevention in AF combined with strict blood pressure control is of primary importance, since stroke risk and bleeding risk are both greater with underlying hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Origin and Evolution of the Sponge Aggregation Factor Gene Family.

PubMed

Grice, Laura F; Gauthier, Marie E A; Roper, Kathrein E; Fernàndez-Busquets, Xavier; Degnan, Sandie M; Degnan, Bernard M

2017-05-01

Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here, we characterize the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic. Further AF variance appears to be generated through individualistic patterns of RNA editing. The AF gene family varies between poriferans, with protein sequences and domains diagnostic of the AF family being present in Amphimedon and other demosponges, but absent from other sponge classes. Within the demosponges, AFs vary widely with no two species having the same AF repertoire or domain organization. The evolution of AFs suggests that their diversification occurs via high allelism, and the continual and rapid gain, loss and shuffling of domains over evolutionary time. Given the marked differences in metazoan allorecognition genes, we propose the rapid evolution of AFs in sponges provides a model for understanding the extensive diversification of self-nonself recognition systems in the animal kingdom. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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.

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.

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.

Left ventricular stiffness estimated by diastolic wall strain is associated with paroxysmal atrial fibrillation in structurally normal hearts.

PubMed

Uetake, Shunsuke; Maruyama, Mitsunori; Yamamoto, Teppei; Kato, Katsuhito; Miyauchi, Yasushi; Seino, Yoshihiko; Shimizu, Wataru

2016-12-01

Left ventricular (LV) diastolic dysfunction depends on an impaired relaxation and stiffness. Abnormal LV relaxation contributes to the development of atrial fibrillation (AF), but the role of LV stiffness in AF remains unclear. Diastolic wall strain (DWS), a load-independent, noninvasive direct measure of LV stiffness, correlates with prevalent AF. This study included 328 consecutive subjects with structurally normal hearts: 164 paroxysmal AF patients and 164 age- and sex-matched (1:1) controls. We calculated the DWS from the M-mode echocardiographic measurements of the LV posterior wall thickness at end-systole and end-diastole during sinus rhythm. The DWS was lower in the AF patients (0.35 ± 0.07) than in the controls (0.41 ± 0.06; P < 0.001). After adjusting for the risk factors of AF using a conditional logistic regression analysis, a history of hypertension, plasma brain-type natriuretic peptide level, and DWS were independently associated with AF prevalence, whereas body mass index, LV mass index, left atrial volume, and any conventional indices of the diastolic function were not. A low DWS (<0.380) was the strongest indicator of AF (odds ratio: 6.22, 95% confidence interval: 3.08-14.2, P < 0.001). Increased LV stiffness estimated by DWS was a strong determinant of the prevalence of AF. LV stiffness may play a role in the pathogenesis of paroxysmal AF in structurally normal hearts. © 2016 Wiley Periodicals, Inc.

Characteristics and Prognosis of Pacemaker-Identified New-Onset Atrial Fibrillation in Japanese People.

PubMed

Ogino, Yutaka; Ishikawa, Toshiyuki; Ishigami, Tomoaki; Matsumoto, Katsumi; Hosoda, Junya; Iguchi, Kouhei; Matsushita, Hirooki; Taguchi, Yuka; Horiguchi, Yoriko; Kimura, Kazuo

2017-05-25

The characteristics and prognosis of implanted pacemaker-identified new-onset atrial fibrillation (AF) in Japanese people has not been well evaluated.Methods and Results:A total of 395 consecutive patients with newly implanted pacemakers were retrospectively analyzed between January 2010 and December 2015 at Yokohama City University Hospital. Patients with a prior history of AF, VVI mode pacemaker, congenital heart disease, severe valvular heart disease, and cardiovascular surgery before pacemaker implantation were excluded. Among the remaining patients, 44 (21.3%) developed new AF during follow-up (mean follow-up, 1,115±651 days; range, 9-2,176 days). Patients with new-onset AF had a significantly higher CHADS 2 score (2.09±1.27 vs. 1.31±1.08, P<0.001) and CHA 2 DS 2 -VASc score (3.00±1.39 vs. 2.26±1.19, P<0.001) compared with those without new-onset AF. On Cox regression analysis only age at implantation was significantly correlated with new-onset AF. Interestingly, the incidence of hospitalization due to heart failure was significantly higher in the new-onset AF than in the without new-onset AF group. A total of 21.3% of pacemaker-implanted patients with high CHADS 2 and CHA 2 DS 2 -VASc scores developed new-onset AF during a mean follow-up of 3.1 years; and pacemaker-identified AF was associated with an increased risk of worsening heart failure.

Amniotic fluid stem cells provide considerable advantages in epidermal regeneration: B7H4 creates a moderate inflammation microenvironment to promote wound repair.

PubMed

Sun, Qing; Li, Fang; Li, Hong; Chen, Rui-Hua; Gu, Yan-Zheng; Chen, Ying; Liang, Han-Si; You, Xin-Ran; Ding, Si-Si; Gao, Ling; Wang, Yun-Liang; Qin, Ming-De; Zhang, Xue-Guang

2015-06-23

The current treatments for severe skin injury all involve skin grafting. However, there is a worldwide shortage of donor skin tissue. In this study, we examined the advantages of using human amniotic fluid stem (hAFS) cells in skin wound healing. In vitro, hAFS cells differentiate into keratinocytes (termed hAFS-K). Like keratinocytes, hAFS-K cells express the markers K5, K14, K10 and involucrin; display typical cellular structure, including a tonofibril-rich cytoplasm; and construct a completely pluristratified epithelium in 3D culture. In vivo, in a mouse excisional wound model, GFP-positive hAFS cells participate in wound repair. Co-localization of GFP/K14 and GFP/K10 in the repaired epidermis demonstrated that hAFS cells can differentiate into keratinocytes. Real-time PCR results confirmed that hAFS cells can initiate and promote early-stage repair of skin damage. During wound repair, hAFS cells did not directly secrete repair-related factors, such as bFGF, VEGF, CXCL12, TGF-β1 and KGF, and provided a moderate inflammation reaction with lower expression of IL-1β, IL-6, TNF-α, Cox2 and Mac3. In hAFS cells, the negative co-stimulatory molecule B7H4 regulates low immunogenicity, which can provide a modest inflammatory reaction microenvironment for wound repair. Furthermore, with their uniquely high proliferation rate, hAFS cells offer a promising alternative for epidermal regeneration.

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.

A KCNQ1 mutation causes age-dependant bradycardia and persistent atrial fibrillation.

PubMed

Ki, Chang-Seok; Jung, Chae Lim; Kim, Hyun-ji; Baek, Kwan-Hyuck; Park, Seung Jung; On, Young Keun; Kim, Ki-Suk; Noh, Su Jin; Youm, Jae Boum; Kim, June Soo; Cho, Hana

2014-03-01

Atrial fibrillation (AF) is the most common arrhythmia. Gain-of-function mutations in KCNQ1, the pore-forming α-subunit of the slow delayed rectifier K current (IKs) channel, have been associated with AF. The purpose of this study was functional assessment of a mutation in KCNQ1 identified in a family with persistent AF and sinus bradycardia. We investigated whether this KCNQ1 missense mutation could form the genetic basis for AF and bradycardia simultaneously in this family. Sanger sequencing in a family with hereditary persistent AF identified a novel KCNQ1 variant (V241F) in a highly conserved region of S4 domain. The proband and her son developed bradycardia and persistent AF in an age-dependent fashion. The other son was a mutation carrier but he showed sinus bradycardia and not AF. Whole-cell patch clamp electrophysiology showed that V241F mutation in KCNQ1 shifted the activation curve to the left and dramatically slowed deactivation, leading to a constitutively open-like phenotype. Computer modeling showed that V241F would slow pacemaker activity. Also, simulations of atrial excitation predicted that V241F results in extreme shortening of action potential duration, possibly resulting in AF. Our study indicates that V241F might cause sinus bradycardia by increasing IKs. Additionally, V241F likely shortens atrial refractoriness to promote a substrate for reentry. KCNQ1 mutations have previously been described in AF, yet this is the first time a mutation in KCNQ1 is associated with age-dependent bradycardia and persistent AF. This finding further supports the hypothesis that sinus node dysfunction contributes to the development of AF.

Fundus autofluorescence findings in central serous chorioretinopathy using two different confocal scanning laser ophthalmoscopes: correlation with functional and structural status.

PubMed

Shin, Joo Youn; Choi, Hun Jin; Lee, Jonghyun; Choi, Moonjung; Chung, Byunghoon; Byeon, Suk Ho

2016-08-01

To compare autofluorescence (AF) findings using wide-field (Optomap) and conventional (HRA-AF) confocal scanning laser ophthalmoscopy (cSLO) systems in patients with central serous chorioretinopathy (CSC), and to investigate the correlations between AF findings and functional and anatomical status. Optical coherence tomography (OCT) and AF images were compared in 73 eyes with serous retinal detachment (SRD) (group A) and 30 eyes without SRD (group B). We evaluated AF findings from the SRD region, atrophic area, and foveola. Correlations between AF findings and outer retinal abnormalities in OCT and visual acuity (VA) were analyzed. Optomap-AF was more effective than HRA-AF in identifying the margins of a detached area (P = 0.001) in group A, and for monitoring mild outer retinal damage (P = 0.041) in group B. The foveolar AF grades in both instruments were significantly correlated with VA and central foveal thickness (CFT) in both group A (Optomap, VA r s = 0.33, P = 0.012; CFT r s = -0.38, P = 0.002; HRA, VA r s = 0.62, P < 0.001; CFT r s = -0.70, P < 0.001) and group B (Optomap, VA r s = 0.71, P < 0.001, CFT r s = -0.78, P < 0.001; HRA, VA r s = 0.40, P = 0.026, CFT r s = -0.40, P = 0.030). Optomap-AF was found to be advantageous for monitoring subretinal status in eyes with SRD, and more accurately reflected mild outer retinal changes in eyes without SRD. Foveolar AF grades of both imaging modalities were significantly correlated with functional and anatomical status.

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.

Lean body mass and risk of incident atrial fibrillation in post-menopausal women

PubMed Central

Azarbal, Farnaz; Stefanick, Marcia L.; Assimes, Themistocles L.; Manson, JoAnn E.; Bea, Jennifer W.; Li, Wenjun; Hlatky, Mark A.; Larson, Joseph C.; LeBlanc, Erin S.; Albert, Christine M.; Nassir, Rami; Martin, Lisa W.; Perez, Marco V.

2016-01-01

Aims High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. Methods and results The Women's Health Initiative is a study of post-menopausal women aged 50–79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14–1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31–1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19–1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13–1.31). Conclusion Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF. PMID:26371115

Mechanisms of Atrial Fibrillation: Rotors, Ionic Determinants and Excitation Frequency

PubMed Central

Berenfeld, Omer; Jalife, José

2017-01-01

Summary Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. However its mechanisms are poorly understood and AF therapy is often sub-optimal. This article reviews recent experimental, numerical and clinical data on dynamics of wave propagation during AF and its mechanistic link to ionic and structural properties of the atria. At the outset, we review numerical and optical mapping data suggesting that the sustained activity of periodic drivers (rotors) with exceedingly high dominant frequencies (DF) of excitation underlies the spatial dispersion and irregularity of activation rates that characterize AF. We show how optical mapping of the fibrillating atria in isolated normal sheep hearts has revealed that the rotors tend to localize in the left atrium (LA). We then discuss exciting new data in the sheep model of tachypacing induced AF demonstrating that the DF of paroxysmal AF episodes increases progressively over days or weeks during the transition to persistent AF (PeAF) and that the rate of the DF increase predicts the onset of PeAF. The data show that the DF increase during the transition may be explained by rotor acceleration secondary to upregulation of IK1 and downregulation of ICaL. The article concludes with a discussion on how translation of experimentally derived knowledge on the behavior and frequency of rotors may find its way into the clinic. We focus on studies in which the analysis of the spatial patterns of DF distribution in the atria of patients with paroxysmal vs persistent has increased our understanding of human AF and how that knowledge might contribute to improve the outcome of AF ablation procedures. PMID:26968663

Pulmonary Embolism and Atrial Fibrillation: Two Sides of the Same Coin? A Systematic Review.

PubMed

Bikdeli, Behnood; Abou Ziki, Maen D; Lip, Gregory Y H

2017-11-01

Pulmonary embolism (PE) is a common, potentially fatal thrombotic disease. Atrial fibrillation (AF), the most common arrhythmia, may also lead to thromboembolic complications. Although initially appearing as distinct entities, PE and AF may coexist. The direction and extent of this association has not been well characterized. We performed a search of PubMed, Scopus, and the Cochrane Database of Systematic Reviews for publications that reported coexisting AF in patients with PE, or vice versa, to provide a systematic overview of pathophysiological and epidemiological aspects of this association (last search: October 13, 2016). We screened 650 articles following the PubMed search, and 697 through Scopus. PE and AF share many common risk factors, including old age, obesity, heart failure, and inflammatory states. In addition, PE may lead to AF through right-sided pressure overload or inflammatory cytokines. AF, in turn, might lead to right atrial appendage clot formation and thereby PE. Epidemiological studies indicate that AF can be seen as a presenting sign, during the early phase, or later in the course of recovery from PE. Patients with AF are also at increased risk of developing PE, a risk that correlates with the CHA 2 DS 2 -VASc score. For the choice of antithrombotic therapy, PE-related factors (provoked or unproved, active cancer, and prior recurrence) and AF-related factors (CHA 2 DS 2 -VASc score), risk of bleeding, and patient preferences should be considered. In conclusion, PE and AF may coexist, with an understudied bidirectional association. Prognostication and choice of antithrombotic therapy in patients with both PE and AF might be different compared with those who present with only one of the two and warrants further investigation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Healthcare Resource Utilization and Costs Associated with Recurrent Episodes of Atrial Fibrillation: The FRACTAL Registry

PubMed Central

REYNOLDS, MATTHEW R.; ESSEBAG, VIDAL; ZIMETBAUM, PETER; COHEN, DAVID J.

2007-01-01

Cost of Recurrent AF Introduction Drivers of cost in the atrial fibrillation (AF) population are not fully understood. We sought to characterize the resource utilization and costs of treating new-onset AF, with emphasis on the incremental costs associated with recurrent episodes of AF over time. Methods and Results An inception cohort of 973 AF patients was followed at 3–6 month intervals in an observational registry over a mean of 24 ± 9 months. AF therapies, clinical outcomes, and both inpatient and outpatient medical resource utilization were tracked at each follow-up interval. Registry patients were managed primarily with cardioversion and pharmacological therapy. Direct healthcare costs were calculated from a U.S. perspective by multiplying measures of resource utilization by representative price weights. Costs were compared among patients in whom the initial episode of AF became permanent and patients who initially achieved sinus rhythm and had either 0, 1–2, or ≥3 documented recurrences during follow-up. Mean annual costs for these four groups were $2,372, $3,385, $6,331, and $10,312 per patient per year, respectively (P < 0.001 for trend), with the largest variation related to hospital costs. In multivariable analysis controlling for demographic characteristics and baseline cardiac and comorbid conditions, each documented recurrence of AF was found to increase annual healthcare costs by ∼$1,600. Conclusion Following initial diagnosis, patients with AF treated with traditional therapies incur $4,000–$5,000 in annual direct healthcare costs. Costs are markedly higher in patients with multiple AF recurrences. These data may be helpful in evaluating the economic impact of new technologies for treating AF. PMID:17451468

Telomere Length and the Risk of Atrial Fibrillation: Insights into the Role of Biological versus Chronological Aging

PubMed Central

Roberts, Jason D.; Dewland, Thomas A.; Longoria, James; Fitzpatrick, Annette L.; Ziv, Elad; Hu, Donglei; Lin, Jue; Glidden, David V.; Psaty, Bruce M.; Burchard, Esteban G.; Blackburn, Elizabeth H.; Olgin, Jeffrey E.; Heckbert, Susan R.; Marcus, Gregory M.

2014-01-01

Background Advanced age is the most important risk factor for atrial fibrillation (AF), however the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length (ATL) and LTL in cardiac surgery patients. Methods and Results Mean LTL and the TERT rs2736100 single nucleotide polymorphism (SNP) were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of ATL versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF prior to and after adjustment for potential confounders (adjusted hazard ratio [HR] 1.09; 95% CI: 0.92–1.29, p=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 SNP and incident AF (adjusted HR: 0.95; 95% CI: 0.88–1.04, p=0.265). In 35 cardiac surgery patients (26 with AF), ATL was longer than LTL (1.19 ± 0.20 versus 1.02 ± 0.25 [T/S ratio], p< 0.001), a finding that remained consistent within the AF subgroup. Conclusions Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF. PMID:25381796

Late outcomes after the Cox maze IV procedure for atrial fibrillation.

PubMed

Henn, Matthew C; Lancaster, Timothy S; Miller, Jacob R; Sinn, Laurie A; Schuessler, Richard B; Moon, Marc R; Melby, Spencer J; Maniar, Hersh S; Damiano, Ralph J

2015-11-01

The Cox maze IV procedure (CMPIV) has been established as the gold standard for surgical ablation; however, late outcomes using current consensus definitions of treatment failure have not been well described. To compare to reported outcomes of catheter-based ablation, we report our institutional outcomes of patients who underwent a left-sided or biatrial CMPIV at 5 years of follow-up. Between January 2002 and September 2014, data were collected prospectively on 576 patients with AF who underwent a CMPIV (n = 532) or left-sided CMPIV (n = 44). Perioperative variables and long-term freedom from AF, with and without AADs, were compared in multiple subgroups. Follow-up at any time point was 89%. At 5 years, overall freedom from AF was 93 of 119 (78%), and freedom from AF off AADs was 77 of 177 (66%). No differences were found in freedom from AF, with or without AADs, at 1, 2, 3, 4, and 5 years for patients with paroxysmal AF (n = 204) versus with persistent/longstanding persistent AF (n = 305), or for those who underwent standalone versus a concomitant CMP. Duration of preoperative AF and hospital length of stay were the best predictors of failure at 5 years. The outcomes of the CMPIV remain good at late follow-up. The type of preoperative AF or the addition of a concomitant procedure did not affect late success. The results of the CMPIV remain superior to those reported for catheter ablation and other forms of surgical AF ablation, especially for patients with persistent or longstanding AF. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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.

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

Model-dependent effects of the gap junction conduction-enhancing antiarrhythmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs.

PubMed

Shiroshita-Takeshita, Akiko; Sakabe, Masao; Haugan, Ketil; Hennan, James K; Nattel, Stanley

2007-01-23

Abnormal intercellular communication caused by connexin dysfunction may be involved in atrial fibrillation (AF). The present study assessed the effect of the gap junctional conduction-enhancing peptide rotigaptide on AF maintenance in substrates that result from congestive heart failure induced by 2-week ventricular tachypacing (240 bpm), atrial tachypacing (ATP; 400 bpm for 3 to 6 weeks), and isolated atrial myocardial ischemia. Electrophysiological study and epicardial mapping were performed before and after rotigaptide administration in dogs with ATP and congestive heart failure, as well as in similarly instrumented sham dogs that were not tachypaced. For atrial myocardial ischemia, dogs administered rotigaptide before myocardial ischemia were compared with no-drug myocardial ischemia controls. ATP significantly shortened the atrial effective refractory period (P=0.003) and increased AF duration (P=0.008), with AF lasting >3 hours in all 6-week ATP animals. Rotigaptide increased conduction velocity in ATP dogs slightly but significantly (P=0.04) and did not affect the effective refractory period, AF duration, or atrial vulnerability. In dogs with congestive heart failure, rotigaptide also slightly increased conduction velocity (P=0.046) but failed to prevent AF promotion. Rotigaptide had no statistically significant effects in sham dogs. Myocardial ischemia alone increased AF duration and impaired conduction (based on conduction velocity across the ischemic border and indices of conduction heterogeneity). Rotigaptide prevented myocardial ischemia-induced conduction slowing and AF duration increases. Rotigaptide improves conduction in various AF models but suppresses AF only for the acute ischemia substrate. These results define the atrial antiarrhythmic profile of a mechanistically novel antiarrhythmic drug and suggest that gap junction dysfunction may be more important in ischemic AF than in ATP remodeling or congestive heart failure substrates.

Atrial Fibrillation and Pulmonary Venous Electrical Conduction Recovery After Full Surgical Resection and Anastomosis of the Pulmonary Veins: Insights From Follow-Up and Ablation Procedures in Lung Transplant Recipients.

PubMed

Hussein, Ayman A; Panchabhai, Tanmay S; Budev, Marie M; Tarakji, Khaldoun; Barakat, Amr F; Saliba, Walid; Lindsay, Bruce; Wazni, Oussama M

2017-06-01

The authors report their experience with atrial fibrillation (AF) rates and ablation findings in lung transplant recipients. Pulmonary venous (PV) conduction recovery accounts for most failed atrial fibrillation (AF) catheter ablation procedures. Lung transplantation involves full surgical resection and replacement of the recipient's PVs with donor's PVs, which may represent the ultimate PV ablation. They followed 755 consecutive lung transplant recipients categorized based on transplant status (unilateral vs. bilateral) and pre-transplant AF. In patients without pre-transplant AF (n = 704), late AF (beyond 6 months after transplant) occurred in 2.5% and 3.3% of unilateral or bilateral lung transplants, respectively. In patients with pre-transplant AF (n = 51), AF recurred in 19.4% and 25.0% of bilateral and unilateral transplants, respectively. In a subset of patients who underwent left atrial ablations after transplant for recurrent refractory AF (n = 8), PV conduction recovery across the surgical anastomoses lines was observed in 22 of 26 previously disconnected PVs. Conduction recovery was observed in ≥1 vein in all but 1 patient. Re-isolation of the veins with additional substrate modification/flutter ablations successfully restored and maintained sinus rhythm in 7 of 8 patients. In lung transplant recipients who undergo full surgical resection of the PVs, a prior history of AF was associated with late AF, regardless of whether patients underwent single or bilateral lung transplantation. PV conduction recovery still occurred and was observed in most patients who underwent left atrial ablation procedures for recurrent AF. Copyright © 2017. Published by Elsevier Inc.

Characterization of genome-wide association-identified variants for atrial fibrillation in African Americans.

PubMed

Delaney, Jessica T; Jeff, Janina M; Brown, Nancy J; Pretorius, Mias; Okafor, Henry E; Darbar, Dawood; Roden, Dan M; Crawford, Dana C

2012-01-01

Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown. We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r(2)<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59-7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46-45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls. Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations.

Prospective randomized study to assess the efficacy of site and rate of atrial pacing on long-term progression of atrial fibrillation in sick sinus syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study.

PubMed

Lau, Chu-Pak; Tachapong, Ngarmukos; Wang, Chun-Chieh; Wang, Jing-Feng; Abe, Haruhiko; Kong, Chi-Woon; Liew, Reginald; Shin, Dong-Gu; Padeletti, Luigi; Kim, You-Ho; Omar, Razali; Jirarojanakorn, Kreingkrai; Kim, Yoon-Nyun; Chen, Mien-Cheng; Sriratanasathavorn, Charn; Munawar, Muhammad; Kam, Ruth; Chen, Jan-Yow; Cho, Yong-Keun; Li, Yi-Gang; Wu, Shu-Lin; Bailleul, Christophe; Tse, Hung-Fat

2013-08-13

Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79-1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79-1.74; P=0.69) did not prevent the development of persistent AF. In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00419640.

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.

A Simple Score That Predicts Paroxysmal Atrial Fibrillation on Outpatient Cardiac Monitoring after Embolic Stroke of Unknown Source.

PubMed

Ricci, Brittany; Chang, Andrew D; Hemendinger, Morgan; Dakay, Katarina; Cutting, Shawna; Burton, Tina; Mac Grory, Brian; Narwal, Priya; Song, Christopher; Chu, Antony; Mehanna, Emile; McTaggart, Ryan; Jayaraman, Mahesh; Furie, Karen; Yaghi, Shadi

2018-06-01

Occult paroxysmal atrial fibrillation (AF) is detected in 16%-30% of patients with embolic stroke of unknown source (ESUS). The identification of AF predictors on outpatient cardiac monitoring can help guide clinicians decide on a duration or method of cardiac monitoring after ESUS. We included all patients with ESUS who underwent an inpatient diagnostic evaluation and outpatient cardiac monitoring between January 1, 2013, and December 31, 2016. Patients were divided into 2 groups based on detection of AF or atrial flutter during monitoring. We compared demographic data, clinical risk factors, and cardiac biomarkers between the 2 groups. Multivariable logistic regression was used to determine predictors of AF. We identified 296 consecutive patients during the study period; 38 (12.8%) patients had AF detected on outpatient cardiac monitoring. In a multivariable regression analysis, advanced age (ages 65-74: odds ratio [OR] 2.36, 95% confidence interval [CI] .85-6.52; ages 75 or older: OR 4.08, 95% CI 1.58-10.52) and moderate-to-severe left atrial enlargement (OR 4.66, 95% CI 1.79-12.12) were predictors of AF on outpatient monitoring. We developed the Brown ESUS-AF score: age (65-74 years: 1 point, 75 years or older: 2 points) and left atrial enlargement (moderate or severe: 2 points) with good prediction of AF (area under the curve .725) and was internally validated using bootstrapping. The percentage of patients with AF detected in each score category were as follows: 0: 4.2%; 1: 14.8%; 2: 20.8%; 3: 22.2%; 4: 55.6%. The Brown ESUS-AF score predicts AF on prolonged outpatient monitoring after ESUS. More studies are needed to externally validate our findings. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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.

Left Atrial Size and Left Ventricular End-Systolic Dimension Predict the Progression of Paroxysmal Atrial Fibrillation After Catheter Ablation.

PubMed

Liao, Ying-Chieh; Liao, Jo-Nan; Lo, Li-Wei; Lin, Yenn-Jiang; Chang, Shih-Lin; Hu, Yu-Feng; Chao, Tze-Fan; Chung, Fa-Po; Tuan, Ta-Chuan; Te, Abigail Louise D; Walia, Rohit; Yamada, Shinya; Lin, Chung-Hsing; Lin, Chin-Yu; Chang, Yao-Ting; Allamsetty, Suresh; Yu, Wen-Chung; Huang, Jing-Long; Wu, Tsu-Juey; Chen, Shih-Ann

2017-01-01

Although rare, some paroxysmal atrial fibrillations (AF) still progress despite radiofrequency (RF) ablation. In the study, we evaluated the long-term efficacy of RF ablation and the predictors of AF progression. A total of 589 paroxysmal AF patients (404 men and 185 women; aged 54 ± 12 years) who received 3-dimensional mapping and ablation were enrolled. Their clinical parameters and electrophysiological characteristics were collected. They were divided into Group 1 (N = 13, with AF progression) and Group 2 (N = 576, no AF progression). AF progression was defined as recurrence of persistent AF. Group 1 patients had larger left atrial (LA) diameter, larger left ventricle (LV) end-systolic and end-diastolic diameters, poorer LV systolic function, and more amiodarone use at baseline. After 1.2 ± 0.5 procedures, 123 (21%) patients experienced recurrence during 56 ± 29 months' follow-up. In the multivariate analysis, LA diameter (P = 0.018, HR = 1.12, 95% CI = 1.02-1.24) and LV end-systolic diameter (P = 0.005, HR = 1.10, 95% CI = 1.03-1.17) independently predicted AF progression. LA diameter >43 mm and LV end-systolic diameter >31 mm were the best cut-off values for predicting AF progression by ROC analysis. AF progression rate achieved 19% if they had both larger LA diameter (>43 mm) and LV end-systolic diameter (>31 mm). RF ablation prevents the progression of paroxysmal AF effectively, except in patients with increased LA diameter and LV end-systolic diameter on echocardiogram, suggesting more aggressive rhythm control therapies should be considered in these patients. © 2016 Wiley Periodicals, Inc.

Acute effects of unilateral temporary stellate ganglion block on human atrial electrophysiological properties and atrial fibrillation inducibility.

PubMed

Leftheriotis, Dionyssios; Flevari, Panayota; Kossyvakis, Charalampos; Katsaras, Dimitrios; Batistaki, Chrysanthi; Arvaniti, Chrysa; Giannopoulos, Georgios; Deftereos, Spyridon; Kostopanagiotou, Georgia; Lekakis, John

2016-11-01

In experimental models, stellate ganglion block (SGB) reduces the induction of atrial fibrillation (AF), while data in humans are limited. The aim of this study was to assess the effect of unilateral SGB on atrial electrophysiological properties and AF induction in patients with paroxysmal AF. Thirty-six patients with paroxysmal AF were randomized in a 2:1 order to temporary, transcutaneous, pharmaceutical SGB with lidocaine or placebo before pulmonary vein isolation. Lidocaine was 1:1 randomly infused to the right or left ganglion. Before and after randomization, atrial effective refractory period (ERP) of each atrium, difference between right and left atrial ERP, intra- and interatrial conduction time, AF inducibility, and AF duration were assessed. After SGB, right atrial ERP was prolonged from a median (1st-3rd quartile) of 240 (220-268) ms to 260 (240-300) ms (P < .01) and left atrial ERP from 235 (220-260) ms to 245 (240-280) ms (P < .01). AF was induced by atrial pacing in all 24 patients before SGB, but only in 13 patients (54%) after the intervention (P < .01). AF duration was shorter after SGB: 1.5 (0.0-5.8) minutes from 5.5 (3.0-12.0) minutes (P < .01). Intra- and interatrial conduction time was not significantly prolonged. No significant differences were observed between right and left SGB. No changes were observed in the placebo group. Unilateral temporary SGB prolonged atrial ERP, reduced AF inducibility, and decreased AF duration. An equivalent effect of right and left SGB on both atria was observed. These findings may have a clinical implication in the prevention of drug refractory and postsurgery AF and deserve further clinical investigation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Conventional versus 3-D Echocardiography to Predict Arrhythmia Recurrence After Atrial Fibrillation Ablation.

PubMed

Bossard, Matthias; Knecht, Sven; Aeschbacher, Stefanie; Buechel, Ronny R; Hochgruber, Thomas; Zimmermann, Andreas J; Kessel-Schaefer, Arnheid; Stephan, Frank-Peter; Völlmin, Gian; Pradella, Maurice; Sticherling, Christian; Osswald, Stefan; Kaufmann, Beat A; Conen, David; Kühne, Michael

2017-06-01

Arrhythmia recurrence after atrial fibrillation (AF) ablation remains high and requires repeat interventions in a substantial number of patients. We assessed the value of conventional and 3-D echocardiography to predict AF recurrence. Consecutive patients undergoing AF ablation by means of pulmonary vein isolation were included in a prospective registry. Echocardiograms were obtained prior to the ablation procedure, and analyzed offline in a standardized manner, including 3-D left atrial (LA) volumetry and determination of LA function and sphericity. The primary endpoint, AF recurrence (>30 seconds) between 3 to 12 months after AF ablation, was independently adjudicated. We included 276 patients (73% male, mean age 59.9 ± 9.9 years). Paroxysmal and persistent AF were present in 178 (64%) and 98 (36%) patients, respectively. Mean left ventricular ejection fraction and indexed LA volume in 3-D (LAVI) were 52 ± 12% and 42 ± 13 mL/m 2 , respectively. AF recurrence was observed in 110 (40%) patients after a single procedure. Median (interquartile range) time to AF recurrence was 123 (92; 236) days. In multivariable Cox regression models, the only predictors for AF recurrence were the minimal, maximal, and indexed 3-D LA volumes, P = 0.024, P = 0.016, and P = 0.014, respectively. Quartile specific analysis of 3-D LAVI showed an HR of 1.885 (95%CI 1.066-3.334; P for trend = 0.015) for the highest compared to the lowest quartile. Our results show the important role of LA volume for the long-term freedom from arrhythmia after AF ablation. These data also highlight the potential of 3-D echocardiography in this context and may facilitate patient selection for AF ablation. © 2017 Wiley Periodicals, Inc.

Adapting detection sensitivity based on evidence of irregular sinus arrhythmia to improve atrial fibrillation detection in insertable cardiac monitors.

PubMed

Pürerfellner, Helmut; Sanders, Prashanthan; Sarkar, Shantanu; Reisfeld, Erin; Reiland, Jerry; Koehler, Jodi; Pokushalov, Evgeny; Urban, Luboš; Dekker, Lukas R C

2017-10-03

Intermittent change in p-wave discernibility during periods of ectopy and sinus arrhythmia is a cause of inappropriate atrial fibrillation (AF) detection in insertable cardiac monitors (ICM). To address this, we developed and validated an enhanced AF detection algorithm. Atrial fibrillation detection in Reveal LINQ ICM uses patterns of incoherence in RR intervals and absence of P-wave evidence over a 2-min period. The enhanced algorithm includes P-wave evidence during RR irregularity as evidence of sinus arrhythmia or ectopy to adaptively optimize sensitivity for AF detection. The algorithm was developed and validated using Holter data from the XPECT and LINQ Usability studies which collected surface electrocardiogram (ECG) and continuous ICM ECG over a 24-48 h period. The algorithm detections were compared with Holter annotations, performed by multiple reviewers, to compute episode and duration detection performance. The validation dataset comprised of 3187 h of valid Holter and LINQ recordings from 138 patients, with true AF in 37 patients yielding 108 true AF episodes ≥2-min and 449 h of AF. The enhanced algorithm reduced inappropriately detected episodes by 49% and duration by 66% with <1% loss in true episodes or duration. The algorithm correctly identified 98.9% of total AF duration and 99.8% of total sinus or non-AF rhythm duration. The algorithm detected 97.2% (99.7% per-patient average) of all AF episodes ≥2-min, and 84.9% (95.3% per-patient average) of detected episodes involved AF. An enhancement that adapts sensitivity for AF detection reduced inappropriately detected episodes and duration with minimal reduction in sensitivity. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology

The Role of Pharmacogenetics in Atrial Fibrillation Therapeutics: Is Personalized Therapy in Sight?

PubMed

Darbar, Dawood

2016-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide requiring therapy. Despite recent advances in catheter-based and surgical therapy, antiarrhythmic drugs (AADs) remain the mainstay of treatment for symptomatic AF. However, response in individual patients is highly variable with over half the patients treated with rhythm control therapy experiencing recurrence of AF within a year. Contemporary AADs used to suppress AF are incompletely and unpredictably effective and associated with significant risks of proarrhythmia and noncardiac toxicities. Furthermore, this "one-size" fits all strategy for selecting antiarrhythmics is based largely on minimizing risk of adverse effects rather than on the likelihood of suppressing AF. The limited success of rhythm control therapy is in part due to heterogeneity of the underlying substrate, interindividual differences in disease mechanisms, and our inability to predict response to AADs in individual patients. Genetic studies of AF over the past decade have revealed that susceptibility to and response to therapy for AF is modulated by the underlying genetic substrate. However, the bedside application of these new discoveries to the management of AF patients has thus far been disappointing. This may in part be related to our limited understanding about genetic predictors of drug response in general, the challenges associated with determining efficacy of response to AADs, and lack of randomized genotype-directed clinical trials. Nonetheless, recent studies have shown that common AF susceptibility risk alleles at the chromosome 4q25 locus modulated response to AADs, electrical cardioversion, and ablation therapy. This monograph discusses how genetic approaches to AF have not only provided important insights into underlying mechanisms but also identified AF subtypes that can be better targeted with more mechanism-based "personalized" therapy.

The Role of Pharmacogenetics in Atrial Fibrillation Therapeutics – Is Personalized Therapy in Sight?

PubMed Central

Darbar, Dawood

2015-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide requiring therapy. Despite recent advances in catheter-based and surgical therapy, antiarrhythmic drugs (AAD) remain the mainstay of treatment for symptomatic AF. However, response in individual patients is highly variable with over half the patients treated with rhythm control therapy experiencing recurrence of AF within a year. Contemporary AADs used to suppress AF are incompletely and unpredictably effective and associated with significant risks of proarrhythmia and non-cardiac toxicities. Furthermore, this ‘one-size’ fits all strategy for selecting antiarrhythmics is based largely on minimizing risk of adverse effects rather than on the likelihood of suppressing AF. The limited success of rhythm-control therapy is in part due to heterogeneity of the underlying substrate, interindividual differences in disease mechanisms, and our inability to predict response to AADs in individual patients. Genetic studies of AF over the last decade have revealed that susceptibility to and response to therapy for AF is modulated by the underlying genetic substrate. However, the bedside application of these new discoveries to the management of AF patients has thus far been disappointing. This may in part be related to our limited understanding about genetic predictors of drug response in general, the challenges associated with determining efficacy of response to AADs and lack of randomized genotype-directed clinical trials. Nonetheless, recent studies have shown that common AF susceptibility risk alleles at the chromosome 4q25 locus modulated response to AADs, electrical cardioversion and ablation therapy. This monograph discusses how genetic approaches to AF have not only provided important insights into underlying mechanisms but also identified AF sub-types that can be better targeted with more mechanism-based ‘personalized’ therapy. PMID:25970841

A Randomised Controlled Trial on the Effect of Nurse-Led Educational Intervention at the Time of Catheter Ablation for Atrial Fibrillation on Quality of Life, Symptom Severity and Rehospitalisation.

PubMed

Bowyer, John L; Tully, Phillip J; Ganesan, Anand N; Chahadi, Fahd K; Singleton, Cameron B; McGavigan, Andrew D

2017-01-01

Atrial Fibrillation (AF) is a common condition associated with impaired quality of life (QOL) and recurrent hospitalisation. Catheter ablation for AF is a well-established treatment for symptomatic patients despite medical therapy. We sought to examine the effect of point specific nurse-led education on QOL, AF symptomatology and readmission rate post AF ablation. Forty-one patients undergoing AF ablation were randomised to Nurse Intervention (NI) versus Control (C), n=22 vs. 19. Both groups were well matched with respect to age, sex and AF subtype. All patients completed SF36 and AF Symptom Checklist, Frequency and Severity Scale questionnaires at baseline and six months post ablation. The NI group underwent nurse education on admission, prior to discharge, and with telephone contact. Baseline SF-36 and AF Symptom Checklist, Frequency and Severity scores were similar. The NI group showed significant differences compared to Control with respect to higher QOL on the SF-36 score of Physical Functioning and Vitality at six months. There were significant improvements in seven components of the AF Symptom Checklist, Frequency and Severity at six months in the NI group with a trend in a further seven. There was no difference in AF related hospital readmissions at six months between C and NI groups (10.5% vs. 13.6%, p=ns). Nurse-led education at time of AF ablation is associated with improved QOL and reduced symptom frequency and severity compared to usual care. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Comparison of Risk of Atrial Fibrillation Among Employed Versus Unemployed (from the REasons for Geographic and Racial Differences in Stroke Study).

PubMed

Soliman, Elsayed Z; Zhang, Zhu-Ming; Judd, Suzanne; Howard, Virginia J; Howard, George

2017-10-15

Involuntary unemployment due to job loss has been associated with increased risk of cardiovascular events. Whether it also is associated with increased risk of atrial fibrillation (AF) is currently unknown. Therefore, we examined this association in 8,812 participants residing mainly in the Southeastern United States (mean age 58.1 ± 7.8 years; 63.2%; women; 43.2% black) with data on employment status who were enrolled in the REasons for Geographic And Racial Differences in Stroke study between 2003 and 2007 after excluding those with voluntary unemployment (retiree, homemakers, and students). AF was identified by electrocardiogram and past medical history at the same period. The cross-sectional association between status and type of unemployment with AF was examined in multivariable logistic regression models. Additional analysis in 4,273 participants without baseline AF and with data on incident AF collected in a follow-up visit occurred after a median of 9.4 years from baseline was also conducted. In a model adjusted for socio-demographics, health insurance, income, perceived stress, and cardiovascular risk factors, unemployment was associated with 60% increased odds of AF (odds ratio [95% confidence interval] 1.60 (1.24, 2.07)). This association was consistent in subgroups stratified by median age, gender, race, education, income, and health insurance status. Similarly, unemployment was associated with AF in those without AF at baseline who developed incident AF (odds ratio [95% confidence interval] 1.54 (1.04, 2.37)). In conclusion, involuntary unemployment is associated with increased risk of AF. This may call for considering socioeconomic determinants such as unemployment as part of the preventive strategies for AF. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Application for the Detection of an Irregular Pulse using an iPhone 4S in Patients with Atrial Fibrillation

PubMed Central

McManus, David D.; Lee, Jinseok; Maitas, Oscar; Esa, Nada; Pidikiti, Rahul; Carlucci, Alex; Harrington, Josephine; Mick, Eric; Chon, Ki H.

2012-01-01

Background Atrial fibrillation (AF) is common and associated with adverse health outcomes. Timely detection of AF can be challenging using traditional diagnostic tools. Smartphone use is increasing and may provide an inexpensive and user-friendly means to diagnose AF. Objective To test the hypothesis that a smartphone-based application could detect an irregular pulse from AF. Methods 76 adults with persistent AF were consented for participation in our study. We obtained pulsatile time series recordings before and after cardioversion using an iPhone 4S camera. A novel smartphone application conducted real-time pulse analysis using 2 statistical methods [Root Mean Square of Successive RR Differences (RMSSD/mean); Shannon Entropy (ShE)]. We examined the sensitivity, specificity, and predictive accuracy of both algorithms using the 12-lead electrocardiogram as the gold standard. Results RMSDD/mean and ShE were higher in participants in AF compared with sinus rhythm. The 2 methods were inversely related to AF in regression models adjusting for key factors including heart rate and blood pressure (β coefficients per SD-increment in RMSDD/mean and ShE were −0.20 and −0.35; p<0.001). An algorithm combining the 2 statistical methods demonstrated excellent sensitivity (0.962), specificity (0.975), and accuracy (0.968) for beat-to-beat discrimination of an irregular pulse during AF from sinus rhythm. Conclusions In a prospectively recruited cohort of 76 participants undergoing cardioversion for AF, we found that a novel algorithm analyzing signals recorded using an iPhone 4S accurately distinguished pulse recordings during AF from sinus rhythm. Data are needed to explore the performance and acceptability of smartphone-based applications for AF detection. PMID:23220686

A novel application for the detection of an irregular pulse using an iPhone 4S in patients with atrial fibrillation.

PubMed

McManus, David D; Lee, Jinseok; Maitas, Oscar; Esa, Nada; Pidikiti, Rahul; Carlucci, Alex; Harrington, Josephine; Mick, Eric; Chon, Ki H

2013-03-01

Atrial fibrillation (AF) is common and associated with adverse health outcomes. Timely detection of AF can be challenging using traditional diagnostic tools. Smartphone use is increasing and may provide an inexpensive and user-friendly means to diagnoseAF. To test the hypothesis that a smartphone-based application could detect an irregular pulse fromAF. Seventy-six adults with persistent AF were consented for participation in our study. We obtained pulsatile time series recordings before and after cardioversion using an iPhone 4S camera. A novel smartphone application conducted real-time pulse analysis using 2 statistical methods: root mean square of successive RR difference (RMSSD/mean) and Shannon entropy (ShE). We examined the sensitivity, specificity, and predictive accuracy of both algorithms using the 12-lead electrocardiogram as the gold standard. RMSDD/mean and ShE were higher in participants in AF than in those with sinus rhythm. The 2 methods were inversely related to AF in regression models adjusting for key factors including heart rate and blood pressure (beta coefficients per SD increment in RMSDD/mean and ShE were-0.20 and-0.35; P<.001). An algorithm combining the 2 statistical methods demonstrated excellent sensitivity (0.962), specificity (0.975), and accuracy (0.968) for beat-to-beat discrimination of an irregular pulse during AF from sinus rhythm. In a prospectively recruited cohort of 76 participants undergoing cardioversion for AF, we found that a novel algorithm analyzing signals recorded using an iPhone 4S accurately distinguished pulse recordings during AF from sinus rhythm. Data are needed to explore the performance and acceptability of smartphone-based applications for AF detection. Copyright © 2013 Heart Rhythm Society. All rights reserved.

Catabolic effects of endothelial cell-derived microparticles on disc cells: Implications in intervertebral disc neovascularization and degeneration.

PubMed

Pohl, Pedro H I; Lozito, Thomas P; Cuperman, Thais; Yurube, Takashi; Moon, Hong J; Ngo, Kevin; Tuan, Rocky S; St Croix, Claudette; Sowa, Gwendolyn A; Rodrigues, Luciano M R; Kang, James D; Vo, Nam V

2016-08-01

Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study, we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 h with 250 µg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3-fold), MMP-3 (4.5-fold) and MMP-13 (5.5-fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1466-1474, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Panoramic Electrophysiological Mapping but not Electrogram Morphology Identifies Stable Sources for Human Atrial Fibrillation

PubMed Central

Narayan, Sanjiv M.; Shivkumar, Kalyanam; Krummen, David E.; Miller, John M.; Rappel, Wouter-Jan

2013-01-01

Background The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE). Methods and Results Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0–3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm2; P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67). Conclusions Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm2, with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF. PMID:23392583

Reference gene selection for molecular studies of dormancy in wild oat (Avena fatua L.) caryopses by RT-qPCR method.

PubMed

Ruduś, Izabela; Kępczyński, Jan

2018-01-01

Molecular studies of primary and secondary dormancy in Avena fatua L., a serious weed of cereal and other crops, are intended to reveal the species-specific details of underlying molecular mechanisms which in turn may be useable in weed management. Among others, quantitative real-time PCR (RT-qPCR) data of comparative gene expression analysis may give some insight into the involvement of particular wild oat genes in dormancy release, maintenance or induction by unfavorable conditions. To assure obtaining biologically significant results using this method, the expression stability of selected candidate reference genes in different data subsets was evaluated using four statistical algorithms i.e. geNorm, NormFinder, Best Keeper and ΔCt method. Although some discrepancies in their ranking outputs were noticed, evidently two ubiquitin-conjugating enzyme homologs, AfUBC1 and AfUBC2, as well as one homolog of glyceraldehyde 3-phosphate dehydrogenase AfGAPDH1 and TATA-binding protein AfTBP2 appeared as more stably expressed than AfEF1a (translation elongation factor 1α), AfGAPDH2 or the least stable α-tubulin homolog AfTUA1 in caryopses and seedlings of A. fatua. Gene expression analysis of a dormancy-related wild oat transcription factor VIVIPAROUS1 (AfVP1) allowed for a validation of candidate reference genes performance. Based on the obtained results it can be recommended that the normalization factor calculated as a geometric mean of Cq values of AfUBC1, AfUBC2 and AfGAPDH1 would be optimal for RT-qPCR results normalization in the experiments comprising A. fatua caryopses of different dormancy status.

Primary prevention of atrial fibrillation: does the atrial lead position influence the incidence of atrial arrhythmias in patients with sinus node dysfunction? Results from the PASTA Trial.

PubMed

Spitzer, Stefan G; Wacker, Petra; Gazarek, Steffen; Malinowski, Klaus; Schibgilla, Volker

2009-12-01

PASTA (pacing of the atria in sinus node disease) is a prospective and randomized trial, assessing the effect of different atrial lead positions on the atrial fibrillation (AF) incidence in patients with sinus node disease (SND). The atrial lead position is randomized to: (a) free right atrial wall, (b) right atrial appendage (RAA), (c) coronary sinus ostium (CS-Os), or (d) dual site right atrial pacing (CS-Os + RAA). The pacemakers (Vitatron Selection 9000 or Prevent AF, Vitatron B.V., Arnhem, The Netherlands) are programmed in DDDR 70 mode and the total follow-up duration is 24 months. To describe the atrial rhythm state, pacemaker-derived data (arrhythmia counter) were assessed for AF episodes. AF was considered as evident, if the AF burden (time in AF related to follow-up interval) was >1% (i.e., 15 min/d). Follow-up data after 24 months were evaluated. The analysis evaluates 142 patients (77 male, 74.5 +/- 7.8 years). There was no statistical significant difference with respect to the occurrence of AF between the four groups after 24 months (A: 36%; B: 38%, C: 32%, D: 48%). The percentage of atrial/ventricular pacing was in A: 78/76%, in B: 84/81%, in C: 70/65%, and in D: 79/69%. These differences were not significant. The evaluation of the AF burden >1% and the total AF burden after 24 months did not show differences in the incidence of AF in patients with dual chamber pacemaker therapy for SND. We were not able to demonstrate a significant influence of right atrial lead position on the incidence of AF recurrence.

Comparison of Left Atrial Voltage between Sinus Rhythm and Atrial Fibrillation in Association with Electrogram Waveform.

PubMed

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2017-05-01

The efficacy of low-voltage-guided ablation in addition to pulmonary vein (PV) isolation for atrial fibrillation (AF) has been reported with voltage mapping being performed during sinus rhythm (SR) or AF. The study aimed to compare the left atrial voltage between SR and AF in association with the electrogram waveform. This prospective observational study included 30 consecutive patients with persistent AF. After completion of PV isolation, electrogram points were taken during both SR and AF at the identical locations evenly throughout the left atrium. Electrograms were divided into two types: normal (sharp electrogram with ≤3 peaks or duration <50 ms) and fractionated (>3 peaks and duration ≥50 ms). During SR, 14 (47%) patients had low-voltage (0.5 mV) substrate with an area of 6.8 ± 4.5 cm 2 . In a total of 1,063 point pairs, 135 (13%) demonstrated a fractionated electrogram during SR and 483 (45%) during AF. The locations with fractionated electrograms during AF more frequently showed fractionation during SR compared to those with normal electrograms during AF (23% vs 5%, P < 0.0001), and had lower amplitude during SR (1.47 ± 1.29 mV vs 2.03 ± 1.19 mV, P < 0.0001). Electrogram amplitude was higher during SR than that during AF (1.77 ± 1.27 mV vs 0.96 ± 0.77 mV, P < 0.0001) with a weak correlation (r = 0.56, P < 0.0001). Subgroup analyses revealed that the correlation was relatively strong (r = 0.73, P < 0.0001) among the electrogram amplitudes with normal waveform during SR and AF. Significant differences in electrogram voltage and fractionation degree may exist between SR and AF at the same locations in patients with persistent AF. © 2017 Wiley Periodicals, Inc.

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.

Functional Tricuspid Regurgitation Caused by Chronic Atrial Fibrillation: A Real-Time 3-Dimensional Transesophageal Echocardiography Study.

PubMed

Utsunomiya, Hiroto; Itabashi, Yuji; Mihara, Hirotsugu; Berdejo, Javier; Kobayashi, Sayuki; Siegel, Robert J; Shiota, Takahiro

2017-01-01

Functional tricuspid regurgitation (TR) with a structurally normal tricuspid valve (TV) may occur secondary to chronic atrial fibrillation (AF). However, the clinical and echocardiographic differences according to functional TR subtypes are unclear. Therefore, characterization of functional TR because of chronic AF (AF-TR) remains undetermined. To investigate the prevalence of AF-TR, 437 patients with moderate to severe TR underwent 3-dimensional (3D) transesophageal echocardiography. TR severity was determined by the averaged vena contracta width on apical and parasternal inflow views. The prevalence of AF-TR was 9.2%, whereas that of functional TR because of left-sided heart disease was 45.3%. Clinical features of AF-TR included advanced age, female sex, greater right atrial than left atrial enlargement and lower systolic pulmonary artery pressure compared with left-sided heart disease-TR with sinus rhythm (all P<0.05). In 3D TV assessment, patients with AF-TR had a larger TV annular area with weaker annular contraction (both P<0.001) but a smaller tethering angle (P<0.001) despite a similar leaflet coaptation status compared with patients with left-sided heart disease-TR with sinus rhythm. On multivariable analysis, only the TV annular area in midsystole (coefficient, 0.059; 95% confidence interval, 0.041-0.078 per 100 mm 2 ; P<0.001) was associated with TR severity in AF-TR. The annular area was more closely correlated with the right atrial volume than right ventricular end-systolic volume in AF-TR (P<0.001). AF-TR is not rare and is associated with advanced age and right atrial enlargement. TV deformations and their association with right heart remodeling differ between AF-TR and left-sided heart disease-TR. Our results suggest that in patients with TR secondary to AF, TV annuloplasty should be effective because this entity has annular dilatation without leaflet deformation. © 2017 American Heart Association, Inc.

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.

Increased expression of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in human atria during atrial fibrillation.

PubMed

De-An, Pei; Li, Li; Zhi-Yun, Xu; Jin-Yu, Huang; Zheng-Ming, Xu; Min, Wang; Qiang, Yao; Shi-Eng, Huang

2010-01-01

Atrialfibrillation (AF) is associated with the activation of the renin-angiotensin-aldosterone system in the atria. It is not clear whether the expression of a mineralocorticoid receptor (MR), or 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), conferring aldosterone specificity to the MR, in patients with AF is altered. Patients with AF may be associated with increased expression of MR and 11betaHSD2 in the atria. Atrial tissue samples of 25 patients with rheumatic heart valve disease undergoing a valve replacement operation were examined. A total of 13 patients had chronic persistent AF (>6 mo) and 12 patients had no history of AF. The MR and 11betaHSD2 expression were analyzed at the mRNA and protein level. The localization of MR and 11betaHSD2 in atrial tissue was performed using specific immunohistochemistry staining. The results of real-time quantitative polymerase chain reaction (PCR) showed that AF groups, in comparison with sinus rhythm, had a higher mRNA expression level of MR or 11betaHSD2 (all P < 0.01). Both the MR and 11betaHSD2 protein expression level in atrial tissue were also significantly increased in patients with AF compared with patients with sinus rhythm (P < 0.05 or P < 0.01). The immunohistochemical staining of MR or 11betaHSD2 demonstrated that MR and 11betaHSD2 predominately located in the cytoplasm of myocardial cells in the atrium and the intensity and density of immunostaining appeared to be increased in the atria of patients with AF compared to those without AF. Increasing expression of MR and 11betaHSD2 in the atria during AF is one of the molecular mechanisms for development of atrial interstitial fibrosis in patients with AF. These findings may have an important impact on the treatment of AF with aldosterone antagonists. Copyright 2010 Wiley Periodicals, Inc.

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.

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.

The unique self-assembly/disassembly property of Archaeoglobus fulgidus ferritin and its implications on molecular release from the protein cage.

PubMed

Sana, Barindra; Johnson, Eric; Lim, Sierin

2015-12-01

In conventional in vitro encapsulation of molecular cargo, the multi-subunit ferritin protein cages are disassembled in extremely acidic pH and re-assembled in the presence of highly concentrated cargo materials, which results in poor yields due to the low-pH treatment. In contrast, Archaeoglobus fulgidus open-pore ferritin (AfFtn) and its closed-pore mutant (AfFtn-AA) are present as dimeric species in neutral buffers that self-assemble into cage-like structure upon addition of metal ions. To understand the iron-mediated self-assembly and ascorbate-mediated disassembly properties, we studied the iron binding and release profile of the AfFtn and AfFtn-AA, and the corresponding oligomerization of their subunits. Fe(2+) binding and conversion to Fe(3+) triggered the self-assembly of cage-like structures from dimeric species of AfFtn and AfFtn-AA subunits, while disassembly was induced by dissolving the iron core with reducing agents. The closed-pore AfFtn-AA has identical iron binding kinetics but lower iron release rates when compared to AfFtn. While the iron binding rate is proportional to Fe(2+) concentration, the iron release rate can be controlled by varying ascorbate concentrations. The AfFtn and AfFtn-AA cages formed by iron mineralization could be disassembled by dissolving the iron core. The open-pores of AfFtn contribute to enhanced reductive iron release while the small channels located at the 3-fold symmetry axis (3-fold channels) are used for iron uptake. The iron-mediated self-assembly/disassembly property of AfFtn offers a new set of molecular trigger for formation and dissociation of the protein cage, which can potentially regulate uptake and release of molecular cargo from protein cages. Copyright © 2015 Elsevier B.V. All rights reserved.

Socioeconomic status and the incidence of atrial fibrillation in whites and blacks: the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Misialek, Jeffrey R; Rose, Kathryn M; Everson-Rose, Susan A; Soliman, Elsayed Z; Clark, Cari J; Lopez, Faye L; Alonso, Alvaro

2014-08-20

No previous studies have examined the interplay among socioeconomic status, sex, and race with the risk of atrial fibrillation (AF). We prospectively followed 14 352 persons (25% black, 75% white, 55% women, mean age 54 years) who were free of AF and participating in the Atherosclerosis Risk in Communities (ARIC) study. Socioeconomic status was assessed at baseline (1987-1989) through educational level and total family income. Incident AF through 2009 was ascertained from electrocardiograms, hospitalizations, and death certificates. Cox regression was used to estimate hazard ratios and 95% CIs of AF for education and family income. Interactions were tested between socioeconomic status and age, race, or sex. Over a median follow-up of 20.6 years, 1794 AF cases occurred. Lower family income was associated with higher AF risk (hazard ratio 1.45, 95% CI 1.27 to 1.67 in those with income less than $25 000 per year compared with those with $50 000 or more per year). The association between education and AF risk varied by sex (P=0.01), with the lowest education group associated with higher AF risk in women (hazard ratio 1.88, 95% CI 1.55 to 2.28) but not in men (hazard ratio 1.15, 95% CI 0.97 to 1.36) compared with the highest education group. Adjustment for cardiovascular risk factors attenuated the associations. There were no interactions with race or age. Blacks had lower AF risk than whites in all income and education groups. Lower family income was associated with a higher AF risk overall, whereas the impact of education on AF risk was present only in women. Differences in socioeconomic status do not explain the lower risk of AF in blacks compared with whites. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

PubMed

Emelyanova, Larisa; Ashary, Zain; Cosic, Milanka; Negmadjanov, Ulugbek; Ross, Gracious; Rizvi, Farhan; Olet, Susan; Kress, David; Sra, Jasbir; Tajik, A Jamil; Holmuhamedov, Ekhson L; Shi, Yang; Jahangir, Arshad

2016-07-01

Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF. Copyright © 2016 the American Physiological Society.

Josephson-like spin current in junctions composed of antiferromagnets and ferromagnets

NASA Astrophysics Data System (ADS)

Moor, A.; Volkov, A. F.; Efetov, K. B.

2012-01-01

We study Josephson-like junctions formed by materials with antiferromagnetic (AF) order parameters. As an antiferromagnet, we consider a two-band material in which a spin density wave (SDW) arises. This could be Fe-based pnictides in the temperature interval Tc≤T≤TN, where Tc and TN are the critical temperatures for the superconducting and antiferromagnetic transitions, respectively. The spin current jSp in AF/F/AF junctions with a ballistic ferromagnetic layer and in tunnel AF/I/AF junctions is calculated. It depends on the angle between the magnetization vectors in the AF leads in the same way as the Josephson current depends on the phase difference of the superconducting order parameters in S/I/S tunnel junctions. It turns out that in AF/F/AF junctions, two components of the SDW order parameter are induced in the F layer. One of them oscillates in space with a short period ξF,b˜ℏv/H, while the other decays monotonously from the interfaces over a long distance of the order ξN,b=ℏv/2πT (where v, H, and T are the Fermi velocity, the exchange energy, and the temperature, respectively; the subindex “b” denotes the ballistic case). This is a clear analogy with the case of Josephson S/F/S junctions with a nonhomogeneous magnetization where short- and long-range condensate components are induced in the F layer. However, in contrast to the charge Josephson current in S/F/S junctions, the spin current in AF/F/AF junctions is not constant in space, but oscillates in the ballistic F layer. We also calculate the dependence of jSp on the deviation from the ideal nesting in the AF/I/AF junctions. The spin current is maximal in the insulating phase of the AF and decreases in the metallic phase. It turns to zero at the Neel point when the amplitude of the SDW is zero and changes sign for certain values of the detuning parameter.

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 pharmacist-managed anticoagulation services for patients with AF are well documented. Pharmacist-managed antiarrhythmic drug monitoring is a less well-known case management strategy that facilitates early detection and intervention to minimize toxicity. Managed care pharmacists can play an instrumental role in implementing strategies to improve the cost-effectiveness of and outcomes from drug therapy for AF.

Cognitive predictors of adaptive functioning in children with symptomatic epilepsy.

PubMed

Kerr, Elizabeth N; Fayed, Nora

2017-10-01

The current study sought to understand the contribution of the attention and working memory challenges experienced by children with active epilepsy without an intellectual disability to adaptive functioning (AF) while taking into account intellectual ability, co-occurring brain-based psychosocial diagnoses, and epilepsy-related variables. The relationship of attention and working memory with AF was examined in 76 children with active epilepsy with intellectual ability above the 2nd percentile recruited from a tertiary care center. AF was measured using the Scales of Independent Behavior-Revised (SIB-R) and compared with norm-referenced data. Standardized clinical assessments of attention span, sustained attention, as well as basic and more complex working memory were administered to children. Commonality analysis was used to investigate the importance of the variables with respect to the prediction of AF and to construct parsimonious models to elucidate the factors most important in explaining AF. Seventy-one percent of parents reported that their child experienced mild to severe difficulties with overall AF. Similar proportions of children displayed limitations in domain-specific areas of AF (Motor, Social/Communication, Person Living, and Community Living). The reduced models for Broad and domain-specific AF produced a maximum of seven predictor variables, with little loss in overall explained variance compared to the full models. Intellectual ability was a powerful predictor of Broad and domain-specific AF. Complex working memory was the only other cognitive predictor retained in each of the parsimonious models of AF. Sustained attention and complex working memory explained a large amount of the total variance in Motor AF. Children with a previously diagnosed comorbidity displayed lower Social/Communication, Personal Living, and Broad AF than those without a diagnosis. At least one epilepsy-related variable appeared in each of the reduced models, with age of seizure onset and seizure type (generalized or partial) being the main predictors. Intellectual ability was the most powerful predictor of AF in children with epilepsy whose intellectual functioning was above the 2nd percentile. Co-occurring brain-based cognitive and psychosocial issues experienced by children with living epilepsy, particularly complex working memory and diagnosed comorbidities, contribute to AF and may be amenable to intervention. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Test-retest reproducibility of accommodative facility measures in primary school children.

PubMed

Adler, Paul; Scally, Andrew J; Barrett, Brendan T

2018-05-08

To determine the test-retest reproducibility of accommodative facility (AF) measures in an unselected sample of UK primary school children. Using ±2.00 DS flippers and a viewing distance of 40 cm, AF was measured in 136 children (range 4-12 years, average 8.1 ± 2.1) by five testers on three occasions (average interval between successive tests: eight days, range 1-21 days). On each occasion, AF was measured monocularly and binocularly, for two minutes. Full datasets were obtained in 111 children (81.6 per cent). Intra-individual variation in AF was large (standard deviation [SD] = 3.8 cycles per minute [cpm]) and there was variation due to the identity of the tester (SD = 1.6 cpm). On average, AF was greater: (i) in monocular compared to binocular testing (by 1.4 cpm, p < 0.001); (ii) in the second minute of testing compared to the first (by 1.3 cpm, p < 0.001); (iii) in older compared to younger children (for example, AF for 4/5-year-olds was 3.3 cpm lower than in children ≥ 10 years old, p = 0.009); and (iv) on subsequent testing occasions (for example, visit-2 AF was 2.0 cpm higher than visit-1 AF, p < 0.001). After the first minute of testing at visit-1, only 36.9 per cent of children exceeded published normative values for AF (≥ 11 cpm monocularly and ≥ 8 cpm binocularly), but this rose to 83.8 per cent after the third test. Using less stringent pass criteria (≥ 6 cpm monocularly and ≥ 3 cpm binocularly), the equivalent figures were 82.9 and 96.4 per cent, respectively. Reduced AF did not co-exist with abnormal near point of accommodation or reduced visual acuity. The results reveal considerable intra-individual variability in raw AF measures in children. When the results are considered as pass/fail, children who initially exhibit normal AF continued to do so on repeat testing. Conversely, the vast majority of children with initially reduced AF exhibit normal performance on repeat testing. Using established pass/fail criteria, the prevalence of persistently reduced AF in this sample is 3.6 per cent. © 2018 Optometry Australia.

Impaired endothelial function in lone atrial fibrillation.

PubMed

Polovina, Marija; Potpara, Tatjana; Giga, Vojislav; Stepanović, Jelena; Ostojić, Miodrag

2013-10-01

Impaired endothelial function has been previously documented in patients with atrial fibrillation (AF) and underlying comorbidities or older patients with idiopathic AF. The aim of this study was to evaluate systemic endothelial function in younger AF patients (less than < 60 years old) with lone AF (that is, without associated cardiopulmonary comorbidities, including arterial hypertension), by comparing brachial artery flow-mediated dilation (FMD) in lone AF patients with FMD of healthy subjects in sinus rhythm. Two groups of participants were prospectively enrolled. The first group comprised of 38 AF patients (the mean age 45 +/- 11 years, 68% male) with persistent (> 7 days) lone AF. The second group comprised of 28 healthy controls in sinus rhythm (the mean age 43 +/- 13, 53% male), matched by age, gender and atherosclerotic risk factors. All the participants underwent physical examination, laboratory analysis [including determination of C-reactive protein (CRP)], standard echocardiography and exercise-stress testing. Brachial artery FMD and endothelium independent dilation (NMD) were assessed with a high-resolution ultrasound probe and arterial diameters taken from 5 consecutive cardiac cycles were averaged for each measurement to accommodate to beat-to-beat flow variations in AF. There were no differences between the 2 groups regarding age, gender and most clinical, laboratory and echocardiographic characteristics (all p > 0.05), apart from the increased heart rate (p = 0.018), body mass index (p = 0.027), CRP levels (p = 0.007) and left atrial anteroposterior dimension (p < 0.001) in AF patients. FMD of AF patients [median value 5.0%, interquartile range (IQR) 2.87%-7.50%] was significantly lower (p < 0.001) than FMD of healthy controls (median value 8.85%, IQR 5.80%-12.50%), whereas there were no differences in median NMD values (p > 0.05). In the multivariate analysis, the independent FMD determinants in our study population were the presence of AF, smoking and total cholesterol levels (all p < 0.001). In patients with AF, the strongest independent FMD determinant was arrhythmia duration (p < 0.001), followed by smoking (p = 0.013) and total cholesterol levels (p = 0.045). Our findings confirm that sustained AF is associated with systemic endothelial dysfunction even in relatively young patients with no cardiovascular disorders or risk factors. AF is an independent contributor to lower FMD and a prolonged arrhythmia duration may confer the risk for more profound endothelial damage.

[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 Holter recording of atrial premature contractions; 2 of them with permanent AF became paroxysmal in one, and still in AF in the other. Reconduction between the left atrium and the pulmonary veins is the dominant factor for post-LACA ATAs and AF recurrence. Other forms of atrial tachycardias or supraventricular tachycardias may coexist with AF or sometimes trigger AF. LACA can not sufficiently modify AF substrate in some permanent AF patients.

Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

NASA Astrophysics Data System (ADS)

Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

2014-05-01

Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had a greater fraction of their DOM that was more humic-like than the paired non-AfDE samples, though differences were small. Similarly, FTICR-MS analysis of hot water extracts suggests that differences among the three sites analyzed were larger than between the paired AfDE and non-AfDE extracts. Overall, in spite of substantial differences in the composition of bulk SOM, the extractable fractions appear to be relatively similar between the AfDE and non-AfDE soils.

Disk storage at CERN

NASA Astrophysics Data System (ADS)

Mascetti, L.; Cano, E.; Chan, B.; Espinal, X.; Fiorot, A.; González Labrador, H.; Iven, J.; Lamanna, M.; Lo Presti, G.; Mościcki, JT; Peters, AJ; Ponce, S.; Rousseau, H.; van der Ster, D.

2015-12-01

CERN IT DSS operates the main storage resources for data taking and physics analysis mainly via three system: AFS, CASTOR and EOS. The total usable space available on disk for users is about 100 PB (with relative ratios 1:20:120). EOS actively uses the two CERN Tier0 centres (Meyrin and Wigner) with 50:50 ratio. IT DSS also provide sizeable on-demand resources for IT services most notably OpenStack and NFS-based clients: this is provided by a Ceph infrastructure (3 PB) and few proprietary servers (NetApp). We will describe our operational experience and recent changes to these systems with special emphasis to the present usages for LHC data taking, the convergence to commodity hardware (nodes with 200-TB each with optional SSD) shared across all services. We also describe our experience in coupling commodity and home-grown solution (e.g. CERNBox integration in EOS, Ceph disk pools for AFS, CASTOR and NFS) and finally the future evolution of these systems for WLCG and beyond.

The strategic plan of the American Fisheries Society

USGS Publications Warehouse

Johnson, B.L.; Irwin, E.R.; Landolt, M.L.; Loefflad, M.; Marsh, J.; Marshall, T.R.; Olmsted, L.L.; Pajak, P.; Peterson, S.; Webster, J.

1994-01-01

In August 1994, at its annual meeting in Halifax, Nova Scotia, the Executive Committee of the American Fisheries Society (AFS) approved a new Strategic Plan. The plan sets out eight goals that define a vision of AFS in the year 2001, and provides strategies to achieve each goal. Accomplishing the plan should position AFS to be more responsive to member needs and more effective at meeting the challenges facing the resource and profession under future expected conditions. The plan provides opportunities for every member to help shape AFS for the 21st century. In this paper, we describe the process of strategic planning, the goals and strategies of the AFS Strategic Plan, and how the plan is implemented through AFS annual work plans.

Instantly Converting Atrial Fibrillation into Sinus Rhythm by a Digital Rectal Exam on a 29-year-Old Male

PubMed Central

Ruan, Cheng-Huai

2010-01-01

Vagal maneuvers cause increase in vagal tone, which has been shown to slow many types supraventricular tachycardia, such as atrial fibrillation (AF). However, the conversion of AF to sinus rhythm is usually not associated with vagal manuvers. Thus, AF is classically treated with medication and electrical cardioversion. Here, we present a 29-year-old male with no cardiovascular history and a low atherosclerotic risk profile who developed AF which converted into sinus rhythm immediately after a digital rectal exam. The patient remained asymptomatic after a 3-month follow-up. This implies that the digital rectal exam can be considered as an additional attempt to convert AF to sinus rhythm in AF patients. PMID:21769254

Atrial Fibrillation Ablation and its Impact on Stroke.

PubMed

Graves, Kevin G; Jacobs, Victoria; May, Heidi T; Cutler, Michael J; Day, John D; Bunch, T Jared

2018-01-24

Atrial fibrillation (AF) is a commonly encountered arrhythmia, which is not yet fully understood. Catheter ablation has shown to be an effective strategy for rhythm management and several small or retrospective studies have shown that stroke rates are decreased in ablated AF patients compared to those medically managed. Several studies even show that ablation returns stroke risk to that of non-AF patients. Large scale, prospective trials will further illuminate this connection and provide mechanistic understanding of the role of the procedure versus the process of selection for the procedure and peri- and post-procedural therapy and management. Furthermore, modification of risk factors associated with AF show a significant increase in the sustained success of AF ablation and can also moderate the progression of AF.

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.

Physical activity, obesity, weight change, and risk of atrial fibrillation: the Atherosclerosis Risk in Communities study.

PubMed

Huxley, Rachel R; Misialek, Jeffrey R; Agarwal, Sunil K; Loehr, Laura R; Soliman, Elsayed Z; Chen, Lin Y; Alonso, Alvaro

2014-08-01

Physical activity (PA) has previously been suggested to attenuate the risk of atrial fibrillation (AF) conferred by excess body weight and weight gain. We prospectively examined the relationship between body size, weight change, and level of PA in a biracial cohort of middle-aged men and women. Baseline characteristics on risk factor levels were obtained on 14 219 participants from the Atherosclerosis Risk in Communities Study. AF incidence was ascertained from 1987 to 2009. Adjusted Cox proportional hazards models were used to estimate the associations between body mass index, waist circumference, relative weight change, and PA level with incident AF. During follow-up, there were 1775 cases of incident AF. Body mass index and waist circumference were positively associated with AF as was weight loss/gain of >5% initial body weight. An ideal level of PA had a small protective effect on AF risk and partially attenuated the risk of AF associated with excess weight in men but not women: compared with men with a normal body mass index, the risk of AF in obese men with an ideal, intermediate, and poor level of PA at baseline was increased by 37%, 129%, and 156% (Pinteraction=0.04). During follow-up, PA did not modify the association between weight gain and risk of AF. Obesity and extreme weight change are risk factors for incident AF, whereas being physically active is associated with a small reduction in risk. In men only, being physically active offset some, but not all, of the risk incurred with excess body weight. © 2014 American Heart Association, Inc.

Polarimetric imaging of retinal disease by polarization sensitive SLO

NASA Astrophysics Data System (ADS)

Miura, Masahiro; Elsner, Ann E.; Iwasaki, Takuya; Goto, Hiroshi

2015-03-01

Polarimetry imaging is used to evaluate different features of the macular disease. Polarimetry images were recorded using a commercially- available polarization-sensitive scanning laser opthalmoscope at 780 nm (PS-SLO, GDx-N). From data sets of PS-SLO, we computed average reflectance image, depolarized light images, and ratio-depolarized light images. The average reflectance image is the grand mean of all input polarization states. The depolarized light image is the minimum of crossed channel. The ratio-depolarized light image is a ratio between the average reflectance image and depolarized light image, and was used to compensate for variation of brightness. Each polarimetry image is compared with the autofluorescence image at 800 nm (NIR-AF) and autofluorescence image at 500 nm (SW-AF). We evaluated four eyes with geographic atrophy in age related macular degeneration, one eye with retinal pigment epithelium hyperplasia, and two eyes with chronic central serous chorioretinopathy. Polarization analysis could selectively emphasize different features of the retina. Findings in ratio depolarized light image had similarities and differences with NIR-AF images. Area of hyper-AF in NIR-AF images showed high intensity areas in the ratio depolarized light image, representing melanin accumulation. Areas of hypo-AF in NIR-AF images showed low intensity areas in the ratio depolarized light images, representing melanin loss. Drusen were high-intensity areas in the ratio depolarized light image, but NIR-AF images was insensitive to the presence of drusen. Unlike NIR-AF images, SW-AF images showed completely different features from the ratio depolarized images. Polarization sensitive imaging is an effective tool as a non-invasive assessment of macular disease.

PULSESMART: Pulse-based Arrhythmia Discrimination Using a Novel Smartphone Application

PubMed Central

McManus, David D.; Chong, Jo Woon; Soni, Apurv; Saczynski, Jane S.; Esa, Nada; Napolitano, Craig; Darling, Chad E.; Boyer, Edward; Rosen, Rochelle K.; Floyd, Kevin C.; Chon, Ki H.

2015-01-01

Background Atrial fibrillation (AF) is a common and dangerous paroxysmal rhythm abnormality. Smartphones are increasingly used for mobile health applications by older patients at risk for AF and may be useful for AF screening. Objectives To test whether an enhanced smartphone app for AF detection can discriminate between sinus rhythm (SR), AF, premature atrial contractions (PACs) and premature ventricular contractions (PVCs). Methods We analyzed 219 2-minute pulse recordings from 121 participants with AF (n=98), PACs (n=15), or PVCs (n=15) using an iPhone 4S. We obtained pulsatile time series recordings in 91 participants after successful cardioversion to sinus rhythm from pre-existing AF. The PULSESMART app conducted pulse analysis using 3 methods [Root Mean Square of Successive RR Differences; Shannon Entropy; Poincare plot]. We examined the sensitivity, specificity, and predictive accuracy of the app for AF, PAC, and PVC discrimination from sinus rhythm using the 12-lead EKG or 3-lead telemetry as the gold standard. We also administered a brief usability questionnaire to a subgroup (n=65) of app users. Results The smartphone-based app demonstrated excellent sensitivity (0.970), specificity (0.935), and accuracy (0.951) for real-time identification of an irregular pulse during AF. The app also showed good accuracy for PAC (0.955) and PVC discrimination (0.960). The vast majority of surveyed app users (83%) reported that it was “useful” and “not complex” to use. Conclusions A smartphone app can accurately discriminate pulse recordings during AF from sinus rhythm, PACs, and PVCs. PMID:26391728

Thinking outside the Box: Rotor Modulation in the Treatment of Atrial Fibrillation.

PubMed

Sehra, Ruchir; Narayan, Sanjiv M; Hummel, John

2013-01-01

Ablation for atrial fibrillation (AF) is an important and exciting therapy whose results remain suboptimal. Although most clinical trials show that ablation eliminates AF more effectively than medications, it is disappointing that the continued single procedural success remains ≈50% despite the substantial advances that have taken place in imaging, catheter positioning and energy delivery. Focal impulse and rotor modulation (FIRM), on the other hand, offers the opportunity to precisely define and then ablate patient-specific sustaining mechanisms for AF, rather than trying to eliminate all possible AF triggers. For over a decade, electrophysiologists have described cases in which AF terminates after only limited ablation - usually that cannot be explained by 'random' meandering wavelets. Indeed, recent studies from several laboratories show that all forms of clinical AF are typically 'driven' by stable electrical rotors and focal sources, not by multiple meandering waves. FIRM mapping enables an operator to place a catheter at typically 1-3 predicted sites in the atria, and with <5-10 minutes of RF ablation, terminate AF and potentially render it non-inducible. Several independent laboratories have now shown that such FIRM ablation alone can terminate or substantially slow AF in >80% of patients with persistent and paroxysmal AF and increase the single procedure rate of AF elimination from 50% with PV isolation alone to >80%. Ongoing studies hint that FIRM only ablation, enabling ablation times in the range observed for typical atrial flutter, may also achieve these high success rates without subsequent trigger ablation. This review summarizes the current state-of-the-art on FIRM mapping and ablation.

Atrial Fibrillation Screening in Nonmetropolitan Areas Using a Telehealth Surveillance System With an Embedded Cloud-Computing Algorithm: Prospective Pilot Study

PubMed Central

Chen, Ying-Hsien; Hung, Chi-Sheng; Huang, Ching-Chang; Hung, Yu-Chien

2017-01-01

Background Atrial fibrillation (AF) is a common form of arrhythmia that is associated with increased risk of stroke and mortality. Detecting AF before the first complication occurs is a recognized priority. No previous studies have examined the feasibility of undertaking AF screening using a telehealth surveillance system with an embedded cloud-computing algorithm; we address this issue in this study. Objective The objective of this study was to evaluate the feasibility of AF screening in nonmetropolitan areas using a telehealth surveillance system with an embedded cloud-computing algorithm. Methods We conducted a prospective AF screening study in a nonmetropolitan area using a single-lead electrocardiogram (ECG) recorder. All ECG measurements were reviewed on the telehealth surveillance system and interpreted by the cloud-computing algorithm and a cardiologist. The process of AF screening was evaluated with a satisfaction questionnaire. Results Between March 11, 2016 and August 31, 2016, 967 ECGs were recorded from 922 residents in nonmetropolitan areas. A total of 22 (2.4%, 22/922) residents with AF were identified by the physician’s ECG interpretation, and only 0.2% (2/967) of ECGs contained significant artifacts. The novel cloud-computing algorithm for AF detection had a sensitivity of 95.5% (95% CI 77.2%-99.9%) and specificity of 97.7% (95% CI 96.5%-98.5%). The overall satisfaction score for the process of AF screening was 92.1%. Conclusions AF screening in nonmetropolitan areas using a telehealth surveillance system with an embedded cloud-computing algorithm is feasible. PMID:28951384

High intensity focused ultrasound ablation for atrial fibrillation: results from the National Spanish Registry.

PubMed

Reyes, Guillermo; Ruyra, Xavier; Valderrama, Francisco; Jimenez, Antonio; Duran, Dario; Perez, Enrique; Daroca, Tomas; Moya, Javier; Ramirez, Ulises; Aldamiz, Gonzalo

2016-10-01

A National Spanish Registry to compile all patients treated with high intensity focused ultrasound (HIFU) energy for atrial fibrillation (AF) was created to evaluate the safety and efficacy of AF surgical ablation. A national Spanish registry was created, and ten hospitals using HIFU to ablate AF joined it. A total of 412 patients undergoing cardiac surgery between 2006 and February 2013 were included. AF was divided between paroxysmal AF (33%) and persistent AF (67%) with a mean AF duration of 29.3±108.2 months. Mean left atrial diameter was 51.2±6.5 mm. Mean underlying heart disease were aortic valve disease (49.3%), ischemic disease (25.2%) and mitral disease (33.2%) Clinical follow-up of patients and a 6 months postoperative echocardiogram were performed in all patients. A pacemaker implantation was needed in 4.9% of patients with a perioperative stroke in 2.5%. Rhythm at discharge from hospital was sinus rhythm in 58%, AF in 35.9% and atrial flutter in 0.8% of patients. Sinus rhythm restoration at 6, 12, 24 and 36 months follow-up was achieved in 66.1%, 63.8%, 63.9% and 45.9% of patients respectively. Multivariate analysis showed paroxysmal AF and sinus rhythm restoration in the operating theatre as factors related to sinus rhythm long term restoration. The Spanish national registry showed an efficacy of AF ablation with the HIFU Epicor system of 66.1%, 63.8%, 63.9% and 45.9% at 6, 12, 24 and 36 months follow-up. There were no device-related complications.

Interatrial septum versus right atrial appendage pacing for prevention of atrial fibrillation : A meta-analysis of randomized controlled trials.

PubMed

Zhang, L; Jiang, H; Wang, W; Bai, J; Liang, Y; Su, Y; Ge, J

2017-07-28

Interatrial septum (IAS) pacing seems to be a promising strategy for the prevention of atrial fibrillation (AF); however, studies have yielded conflicting results. This meta-analysis was to compare IAS with right atrial appendage (RAA) pacing on the prevention of postpacing AF occurrence. Pubmed, MEDLINE, EMBASE and Web of Science databases were searched through October 2016 for randomized controlled trials comparing IAS with RAA pacing on the prevention of AF. Data concerning study design, patient characteristics and outcomes were extracted. Risk ratio (RR), weighted mean differences (WMD) or standardized mean differences (SMD) were calculated using fixed or random effects models. A total of 12 trials involving 1146 patients with dual-chamber pacing were included. Although IAS was superior to RAA pacing in terms of reducing the number of AF episodes (SMD = -0.29, P = 0.05), AF burden (SMD = -0.41, P = 0.008) and P -wave duration (WMD = -34.45 ms, P < 0.0001), neither permanent AF occurrence (RR = 0.94, P = 0.58) nor recurrences of AF (RR = 0.88, P = 0.36) were reduced by IAS pacing. Nevertheless, no differences were observed concerning all-cause death (RR = 1.04, P = 0.88), procedure-related events (RR = 1.17, P = 0.69) and pacing parameters between IAS and RAA pacing in the follow-up period. IAS pacing is safe and as well tolerated as RAA pacing. Although IAS pacing may fail to prevent permanent AF occurrence and recurrences of AF, it is able to not only improve interatrial conduction, but also reduce AF burden.

Serum and dietary magnesium and incidence of atrial fibrillation in whites and in African Americans--Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Misialek, Jeffrey R; Lopez, Faye L; Lutsey, Pamela L; Huxley, Rachel R; Peacock, James M; Chen, Lin Y; Soliman, Elsayed Z; Agarwal, Sunil K; Alonso, Alvaro

2013-01-01

Low serum magnesium (Mg) has been associated with an increased risk of cardiovascular disease (CVD), including ventricular arrhythmias, but the association between serum or dietary Mg and atrial fibrillation (AF) has not been investigated. A total of 14,290 men and women (75% white; 53% female; mean age, 54 years) free of AF at baseline participating in the Atherosclerosis Risk in Communities study in the United States, were studied. Incident AF cases through 2009 were ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for AF associated with serum and dietary Mg quintiles. Over a median follow-up time of 20.6 years, 1,755 incident AF cases were identified. In multivariate models, lower serum Mg was associated with higher AF risk: compared to individuals in the middle quintile (≥ 0.80-0.83 mmol/L), the HR (95% CI) of AF in quintiles 1, 2, 4, and 5 were 1.34 (1.16-1.54), 0.99 (0.85-1.16), 1.04 (0.90-1.22), and 1.06 (0.91-1.23), respectively. There was no evidence of significant interactions between serum Mg and sex or race. No association between dietary Mg and AF risk was observed. Lower serum Mg was associated with a higher AF risk, and this association was not different between whites and African Americans. Dietary Mg was not associated with AF risk.

Chronotropic Incompetence and Risk of Atrial Fibrillation: The Henry Ford ExercIse Testing (FIT) Project.

PubMed

O'Neal, Wesley T; Qureshi, Waqas T; Blaha, Michael J; Dardari, Zeina A; Ehrman, Jonathan K; Brawner, Clinton A; Soliman, Elsayed Z; Al-Mallah, Mouaz H

2016-11-01

To examine the association between chronotropic incompetence and incident atrial fibrillation (AF). Patients with inadequate heart rate response during exercise may have abnormalities in sinus node function or autonomic tone that predispose to the development of AF. We examined the association between heart rate response and incident AF in 57,402 (mean age=54±13 years, 47% female, 64% white) patients free of baseline AF who underwent exercise-treadmill stress testing from the Henry Ford ExercIse Testing (FIT) Project. Age-predicted maximum heart rate (pMHR) values <85% and chronotropic index values <80% were used to define chronotropic incompetence. Cox regression, adjusting for demographics, cardiovascular risk factors, medications, coronary heart disease, heart failure, and metabolic equivalent of task achieved, was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between chronotropic incompetence and incident AF. Over a median follow-up of 5.0 years (25 th -75 th percentiles=2.6, 7.8), a total of 3,395 (5.9%) participants developed AF. pMHR values <85% were associated with an increased risk for AF development (HR=1.33, 95%CI=1.22, 1.44). Chronotropic index values <80% also were associated with an increased risk of AF (HR=1.28, 95%CI=1.19, 1.38). The associations of pMHR and chronotropic index with AF remained significant with varying cut-off points to define chronotropic incompetence. Our analysis suggests that patients with inadequate heart rate response during exercise have an increased risk for developing AF.

Are left ventricular ejection fraction and left atrial diameter related to atrial fibrillation recurrence after catheter ablation?

PubMed Central

Jin, Xiao; Pan, Jianke; Wu, Huanlin; Xu, Danping

2018-01-01

Abstract Atrial fibrillation (AF), the most common form of arrhythmia, is associated with the prevalence of many common cardiovascular and cerebrovascular diseases. Catheter ablation is considered the first-line therapy for AF; however, AF recurrence is very common after catheter ablation. Studies have been performed to analyze the factors associated with AF recurrence, but none have reached a consistent conclusion on whether left ventricular ejection fraction (LVEF) and left atrial diameter (LA diameter) affect AF recurrence after catheter ablation. The databases PubMed, Embase, and the Cochrane Library were used to search for relevant studies up to September 2017. RevMan 5.3.5 software provided by the Cochrane Collaboration Network was used to conduct this meta-analysis. Thirteen studies involving 2825 patients were included in this meta-analysis. Overall, the results revealed that elevated LA diameter values were significantly associated with AF recurrence in patients after catheter ablation (MD = 2.19, 95% CI: 1.63–2.75, P < .001), while baseline LVEF levels were not significantly positively associated with AF recurrence in patients after catheter ablation (MD = −0.91, 95% CI: −1.18 to 1.67, P = .14). Overall, elevated LA diameter may be associated with AF recurrence after catheter ablation; however, there was no direct relationship between LVEF values and AF recurrence after catheter ablation when baseline LVEF values are normal or mildly decreased. Besides, because of publication bias, further studies should be performed to explore the mechanisms underlying AF recurrence. PMID:29768386

Health Literacy and Awareness of Atrial Fibrillation.

PubMed

Reading, Stephanie R; Go, Alan S; Fang, Margaret C; Singer, Daniel E; Liu, In-Lu Amy; Black, Mary Helen; Udaltsova, Natalia; Reynolds, Kristi

2017-04-11

Atrial fibrillation (AF) is the most common clinically significant arrhythmia in adults and a major risk factor for ischemic stroke. Nonetheless, previous research suggests that many individuals diagnosed with AF lack awareness about their diagnosis and inadequate health literacy may be an important contributing factor to this finding. We examined the association between health literacy and awareness of an AF diagnosis in a large, ethnically diverse cohort of Kaiser Permanente Northern and Southern California adults diagnosed with AF between January 1, 2006 and June 30, 2009. Using self-reported questionnaire data completed between May 1, 2010 and September 30, 2010, awareness of an AF diagnosis was evaluated using the question "Have you ever been told by a doctor or other health professional that you have a heart rhythm problem called atrial fibrillation or atrial flutter?" and health literacy was assessed using a validated 3-item instrument examining problems because of reading, understanding, and filling out medical forms. Of the 12 517 patients diagnosed with AF, 14.5% were not aware of their AF diagnosis and 20.4% had inadequate health literacy. Patients with inadequate health literacy were less likely to be aware of their AF diagnosis compared with patients with adequate health literacy (prevalence ratio=0.96; 95% CI [0.94, 0.98]), adjusting for sociodemographics, health behaviors, and clinical characteristics. Lower health literacy is independently associated with less awareness of AF diagnosis. Strategies designed to increase patient awareness of AF and its complications are warranted among individuals with limited health literacy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Isolation of canine coronary sinus musculature from the atria by radiofrequency catheter ablation prevents induction of atrial fibrillation.

PubMed

Morita, Hiroshi; Zipes, Douglas P; Morita, Shiho T; Wu, Jiashin

2014-12-01

The junction between the coronary sinus (CS) musculature and both atria contributes to initiation of atrial tachyarrhythmias. The current study investigated the effects of CS isolation from the atria by radiofrequency catheter ablation on the induction and maintenance of atrial fibrillation (AF). Using an optical mapping system, we mapped action potentials at 256 surface sites in 17 isolated and arterially perfused canine atrial tissues containing the entire musculature of the CS, right atrial septum, posterior left atrium, left inferior pulmonary vein, and vein of Marshal. Rapid pacing from each site before and after addition of acetylcholine (0.5 μmol/L) was applied to induce AF. Epicardial radiofrequency catheter ablation at CS-atrial junctions isolated the CS from the atria. Rapid pacing induced sustained AF in all tissues after acetylcholine. Microreentry within the CS drove AF in 88% of preparations. Reentries associated with the vein of Marshall (29%), CS-atrial junctions (53%), right atrium (65%), and pulmonary vein (76%) (frequently with 2-4 simultaneous circuits) were additional drivers of AF. Radiofrequency catheter ablation eliminated AF in 13 tissues before acetylcholine (P<0.01) and in 5 tissues after acetylcholine. Radiofrequency catheter ablation also abbreviated the duration of AF in 12 tissues (P<0.01). CS and its musculature developed unstable reentry and AF, which were prevented by isolation of CS musculature from atrial tissue. The results suggest that CS can be a substrate of recurrent AF in patients after pulmonary vein isolation and that CS isolation might help prevent recurrent AF. © 2014 American Heart Association, Inc.

Biaxial mechanics and inter-lamellar shearing of stem-cell seeded electrospun angle-ply laminates for annulus fibrosus tissue engineering.

PubMed

Driscoll, Tristan P; Nakasone, Ryan H; Szczesny, Spencer E; Elliott, Dawn M; Mauck, Robert L

2013-06-01

The annulus fibrosus (AF) of the intervertebral disk plays a critical role in vertebral load transmission that is heavily dependent on the microscale structure and composition of the tissue. With degeneration, both structure and composition are compromised, resulting in a loss of AF mechanical function. Numerous tissue engineering strategies have addressed the issue of AF degeneration, but few have focused on recapitulation of AF microstructure and function. One approach that allows for generation of engineered AF with appropriate (+/-)30° lamellar microstructure is the use of aligned electrospun scaffolds seeded with mesenchymal stem cells (MSCs) and assembled into angle-ply laminates (APL). Previous work indicates that opposing lamellar orientation is necessary for development of near native uniaxial tensile properties. However, most native AF tensile loads are applied biaxially, as the disk is subjected to multi-axial loads and is constrained by its attachments to the vertebral bodies. Thus, the objective of this study was to evaluate the biaxial mechanical response of engineered AF bilayers, and to determine the importance of opposing lamellar structure under this loading regime. Opposing bilayers, which replicate native AF structure, showed a significantly higher modulus in both testing directions compared to parallel bilayers, and reached ∼60% of native AF biaxial properties. Associated with this increase in biaxial properties, significantly less shear, and significantly higher stretch in the fiber direction, was observed. These results provide additional insight into native tissue structure-function relationships, as well as new benchmarks for engineering functional AF tissue constructs. Copyright © 2013 Orthopaedic Research Society.

Age-dependent prognostic significance of atrial fibrillation in outpatients with chronic heart failure: data from the Italian Network on Congestive Heart Failure Registry.

PubMed

Baldasseroni, Samuele; Orso, Francesco; Fabbri, Gianna; De Bernardi, Alberto; Cirrincione, Vincenzo; Gonzini, Lucio; Fumagalli, Stefano; Marchionni, Niccolò; Midi, Paolo; Maggioni, Aldo Pietro

2010-01-01

The role of atrial fibrillation (AF) in older patients with heart failure (HF) is controversial because many variables seem to influence their outcome. We investigated the predictivity of AF in 3 age groups of outpatients with HF. We analyzed 8,178 outpatients enrolled in the Italian Network on Congestive Heart Failure Registry with HF diagnosed according to the European Society of Cardiology criteria. A trained cardiologist established the diagnosis of AF and HF at the entry visit at each center. We stratified the population into 3 age groups, as follows: group A, < or =65 years; group B, 66-75 years, and group C, >75 years. Group A was composed of 4,261 patients, 683 with AF (16.0%); in group B there were 2,651 patients, 638 with AF (24.1%), and group C was composed of 1,266 patients, 412 with AF (32.5%). The 1-year mortality rate was higher in AF patients in all groups. In a multivariate model, AF remained an independent risk factor for death in groups A and B, but not in group C [group A: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.10-1.81; group B: HR 1.29, 95% CI 1.00-1.67; group C: HR 1.05, 95% CI 0.78-1.43]. The prevalence of AF increased with age and was associated with a higher mortality rate. However, AF independently predicted all-cause mortality only in patients aged < or =75 years. Copyright 2010 S. Karger AG, Basel.

Surgical treatment of atrial fibrillation.

PubMed

Pagé, Pierre; Skanes, Allan C

2005-09-01

Surgery aims to eliminate atrial fibrillation (AF) through direct modification of the arrhythmogenic substratum. The Maze procedure, developed two decades ago, has proven to be clearly effective in restoring sinus rhythm in AF patients with or without associated organic cardiac disorders. Indications for surgery may be tailored to the clinical situation involved. In patients with continuous AF associated with structural heart disease (eg, valvular, congenital or coronary artery disease), the performance of a concomitant AF ablation procedure proven to add minimal morbidity to the operation may be highly beneficial to patient outcome. It is likely, although not entirely proven, that the restoration and maintenance of sinus rhythm after mitral valve surgery promotes survival by preventing tachycardia-induced cardiomyopathy and stroke. Novel strategies for AF surgery involve the use of alternate energy sources to create the lines of block in the atria and the simplification of the lesion pattern compared with the earlier Cox-Maze procedure. Published clinical data support the contention that left atrial ablation techniques performed concomitantly with valvular and/or coronary artery bypass surgery are likely to result in a 70% to 90% cure rate of AF in patients with preoperatively documented AF. Despite the lack of evidence for long-term outcome benefit, intraoperative pulmonary vein ablation, feasible with minimal morbidity, clearly appears to be an improvement over simply ignoring AF in patients undergoing cardiac surgery. Left atrial appendectomy appears warranted in patients with chronic persistent AF.

Evaluation of autofluorescence and toluidine blue in the differentiation of oral dysplastic and neoplastic lesions from non dysplastic and neoplastic lesions: a cross-sectional study

NASA Astrophysics Data System (ADS)

Petruzzi, Massimo; Lucchese, Alberta; Nardi, Gianna Maria; Lauritano, Dorina; Favia, Gianfranco; Serpico, Rosario; Grassi, Felice Roberto

2014-07-01

The objective was to compare toluidine blue (TB) and autofluorescence (AF) for the detection of oral dysplasia and squamous cell carcinoma (OSCC) in clinically suspicious lesions according to conventional examination. Fifty-six clinically suspicious lesions were subjected to AF and TB examination. Data were compared using two different scenarios: in the first, mild dysplasia was considered as positive, while in the second, it was considered as negative. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), accuracy, and concordance were calculated. AF sensitivity and specificity were 70.0 and 57.7%, respectively, while TB showed a sensitivity of 80% and a specificity of 61.5%. The sensitivity increased in the second scenario in both AF (76.5%) and TB (88.2%). The specificity decreased in AF and TB, showing the same value (51.3%). PPV was higher in TB than in AF (70.6 versus 65.6%) and similarly for NPV (72.7 versus 62.5%). In the second scenario, TB PPV was 44.1% and NPV was 90.9% AF PPV was 40.6% and NPV was 83.3%. TB showed greater accuracy than AF in the first scenario (62.5 versus 58.9%). AF and TB are both sensitive but not specific in OSCC and dysplasia diagnosis.

[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.

Home of Air National Guard

Science.gov Websites

Force AF announces changes to Courses 14 and 15 AF announces changes to Courses 14 and 15 AF announces changes to Courses 14 and 15 121st ARW recruiter hits career milestone in record time 121st ARW recruiter Force logistics team named best in the Air Force AF announces changes to Courses 14 and 15 RSS More

Defense Small Business Innovation Research Program (SBIR). Volume 1. Army Abstracts of Phase 1 Awards 1992

DTIC Science & Technology

1992-01-01

92NAT-057 1029 CORPORATION WAY Office: NATICK PALO ALTO, CA 94303 Contract #: Phone: (415) 962-9111 P1: Craig A. Grimes Title: Development of Low...INC. AF Topic#: 92-042 ARMY Topic#: 92-139 AF Topic#: 92-066 DEEGAN RESEARCH GROUP, INC. AF Topic#: 92-138 AF Topic#: 92-001 SDIO Topic#: 92-003

Low-dose green tea intake reduces incidence of atrial fibrillation in a Chinese population.

PubMed

Liu, Dong-Chen; Yan, Jian-Jun; Wang, You-Nan; Wang, Ze-Mu; Xie, Zhi-Yong; Ma, Yao; Yang, Yang; Yang, Li; Wang, Lian-Sheng

2016-12-20

The aim of the present study was to assessthe association between green tea intake and incidence of atrial fibrillation (AF) in a Chinese population. A total of 801 (mean age: 62 years; 56% male) subjects were enrolled: 401 AF patients and 400 controls. All subjects completed a questionnaire and the associations between their green tea drinking habits and incidence of AF were assessed using the odds ratio (OR) and binary logistic regression. After multivariate adjustment, green tea intake presented as a protective factor against the incidence of AF (OR: 0.349, 95% CI: 0.253-0.483, P < 0.001). The green tea protection showed downward trend with increasing green tea intake (P for the trend= 0.001). Low frequency, low concentration, short-term tea consumption was classified as low-dose green tea intake. Green tea intake decreased the incidence of both paroxysmal AF (OR: 0.307, 95% CI: 0.216-0.436, P < 0.001) and persistent AF (OR: 0.355, 95% CI: 0.261-0.482, P < 0.001) and may be associated with a decreased incidence of AF. This study suggests that low-dose green tea intake strongly protects against AF.

Atrial fibrillation and gastroesophageal reflux disease: the cardiogastric interaction.

PubMed

Linz, Dominik; Hohl, Mathias; Vollmar, Johanna; Ukena, Christian; Mahfoud, Felix; Böhm, Michael

2017-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Multiple conditions like hypertension, heart failure, diabetes, sleep apnoea, and obesity play a role for the initiation and perpetuation of AF. Recently, a potential association between gastroesophageal reflux disease (GERD) and AF development has been proposed due to the close anatomic vicinity of the oesophagus and the left atrium. As an understanding of the association between acid reflux disease and AF may be important in the global multimodal treatment strategy to further improve outcomes in a subset of patients with AF, we discuss potential atrial arrhythmogenic mechanisms in patients with GERD, such as gastric and subsequent systemic inflammation, impaired autonomic stimulation, mechanical irritation due to anatomical proximity of the left atrium and the oesophagus, as well as common comorbidities like obesity and sleep-disordered breathing. Data on GERD and oesophageal lesions after AF-ablation procedures will be reviewed. Treatment of GERD to avoid AF or to reduce AF burden might represent a future treatment perspective but needs to be scrutinized in prospective trials. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

[Study on the hepatocytic cell targetability of liposomes].

PubMed

Hou, Xin-pu; Wang, Li; Wang, Xiang-tao; Li, Sha

2003-02-01

To target for hepatocytic cell, liposomes was modified by special ligand. Sterically stabilized liposomes (SSL) was conjugated with asialofeticin (AF), the ligand of asialoglycoprotein receptor (ASGP-R) of hepatocyte. ASGP-R-BLM is the ASGP-R reconstructed on bilayer lipid membrane (BLM). The recognition reaction between AF-SSL and ASGP-R-BLM can be monitored by the varieties of membrane electrical parameters. The targetability of AF-SSL mediated to hepatocyte was detected by radioisotopic labeled in vitro and in vivo. The therapeutic effect of antihepatocarcinoma was observed also. The lifetime of ASGP-R-BLM decreased with the added amount of AF-SSL. It was demonstrated that there was recognition reaction between AF-SSL and ASGP-R-BLM. The combination of AF-SSL with hepatocyte was significantly higher than that of SSL without AF-modified in vitro and in vivo. The survival time of rat for AF-SSL carriered ADM (adriamycin) group was much longer and the toxicities on heart, kidney and lung were lower than those SSL carried ADM group. It is possible to actively target the cell with specific receptor by ligand modified liposomes. The result prvide scientific basis of hepatocyte targeted liposomes.

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.

Transient cerebral hypoperfusion and hypertensive events during atrial fibrillation: a plausible mechanism for cognitive impairment

NASA Astrophysics Data System (ADS)

Anselmino, Matteo; Scarsoglio, Stefania; Saglietto, Andrea; Gaita, Fiorenzo; Ridolfi, Luca

2016-06-01

Atrial fibrillation (AF) is associated with an increased risk of dementia and cognitive decline, independent of strokes. Several mechanisms have been proposed to explain this association, but altered cerebral blood flow dynamics during AF has been poorly investigated: in particular, it is unknown how AF influences hemodynamic parameters of the distal cerebral circulation, at the arteriolar and capillary level. Two coupled lumped-parameter models (systemic and cerebrovascular circulations, respectively) were here used to simulate sinus rhythm (SR) and AF. For each simulation 5000 cardiac cycles were analyzed and cerebral hemodynamic parameters were calculated. With respect to SR, AF triggered a higher variability of the cerebral hemodynamic variables which increases proceeding towards the distal circulation, reaching the maximum extent at the arteriolar and capillary levels. This variability led to critical cerebral hemodynamic events of excessive pressure or reduced blood flow: 303 hypoperfusions occurred at the arteriolar level, while 387 hypertensive events occurred at the capillary level during AF. By contrast, neither hypoperfusions nor hypertensive events occurred during SR. Thus, the impact of AF per se on cerebral hemodynamics candidates as a relevant mechanism into the genesis of AF-related cognitive impairment/dementia.

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.

Low-dose green tea intake reduces incidence of atrial fibrillation in a Chinese population

PubMed Central

Wang, Ze-Mu; Xie, Zhi-Yong; Ma, Yao; Yang, Yang; Yang, Li; Wang, Lian-Sheng

2016-01-01

The aim of the present study was to assessthe association between green tea intake and incidence of atrial fibrillation (AF) in a Chinese population. A total of 801 (mean age: 62 years; 56% male) subjects were enrolled: 401 AF patients and 400 controls. All subjects completed a questionnaire and the associations between their green tea drinking habits and incidence of AF were assessed using the odds ratio (OR) and binary logistic regression. After multivariate adjustment, green tea intake presented as a protective factor against the incidence of AF (OR: 0.349, 95% CI: 0.253-0.483, P < 0.001). The green tea protection showed downward trend with increasing green tea intake (P for the trend= 0.001). Low frequency, low concentration, short-term tea consumption was classified as low-dose green tea intake. Green tea intake decreased the incidence of both paroxysmal AF (OR: 0.307, 95% CI: 0.216-0.436, P < 0.001) and persistent AF (OR: 0.355, 95% CI: 0.261-0.482, P < 0.001) and may be associated with a decreased incidence of AF. This study suggests that low-dose green tea intake strongly protects against AF. PMID:27683043

The Need for Increased Critical Technical Skills: Integrating Federal Aviation Administration Airframe and Powerplant Certification in Aircraft Maintenance Force Development

DTIC Science & Technology

2011-12-18

Joaquin Valley College. On-line, Internet. Available at http://www.sjvc.edu/program/Aviation_Maintenance_Technology/ Kansas State University- Salinas ...systems. $- $5,000 $10,000 $15,000 $20,000 $25,000 $30,000 $35,000 $40,000 $45,000 Broward College San Joaquin Valley ...40,000 $45,000 AF A&P Certification Program Broward College San Joaquin Valley College Kansas State University Redstone College

QUest for the Arrhythmogenic Substrate of Atrial fibRillation in Patients Undergoing Cardiac Surgery (QUASAR Study): Rationale and Design.

PubMed

van der Does, Lisette J M E; Yaksh, Ameeta; Kik, Charles; Knops, Paul; Lanters, Eva A H; Teuwen, Christophe P; Oei, Frans B S; van de Woestijne, Pieter C; Bekkers, Jos A; Bogers, Ad J J C; Allessie, Maurits A; de Groot, Natasja M S

2016-06-01

The heterogeneous presentation and progression of atrial fibrillation (AF) implicate the existence of different pathophysiological processes. Individualized diagnosis and therapy of the arrhythmogenic substrate underlying AF may be required to improve treatment outcomes. Therefore, this single-center study aims to identify the arrhythmogenic areas underlying AF by intra-operative, high-resolution, multi-site epicardial mapping in 600 patients with different heart diseases. Participants are divided into 12 groups according to the underlying heart diseases and presence of prior AF episodes. Mapping is performed with a 192-electrode array for 5-10 s during sinus rhythm and (induced) AF of the entire atrial surface. Local activation times are converted into activation and wave maps from which various electrophysiological parameters are derived. Postoperative cardiac rhythm registrations and a 5-year follow-up will show the incidence of postoperative and persistent AF. This project provides the first step in the development of a tool for individual AF diagnosis and treatment.

Role of Rotors in the Ablative Therapy of Persistent Atrial Fibrillation

PubMed Central

Schricker, Amir A; Zaman, Junaid; Narayan, Sanjiv M

2015-01-01

Atrial fibrillation (AF) ablation is increasingly used to maintain sinus rhythm yet its results are sub-optimal, especially in patients with persistent AF or prior unsuccessful procedures. Attempts at improvement have often targeted substrates that sustain AF after it is triggered, yet those mechanisms are debated. Many studies now challenge the concept that AF is driven by self-sustaining disordered wavelets, showing instead that localised drivers (rotors) may drive disorder via a process known as fibrillatory conduction. Novel mapping using wide-area recordings, physiological filtering and phase analysis demonstrates rotors in human AF. Contact mapping with focal impulse and rotor modulation (FIRM) shows that localised ablation at sources can improve procedural success in many populations on long-term follow up and some newer approaches to rotor mapping are qualitatively similar. This review critically evaluates the data on rotor mapping and ablation, which advances our conceptual understanding of AF and holds the promise of substantially improving ablative outcomes in patients with persistent AF. PMID:26835100

Minimally Invasive Delivery of Hydrogel-Encapsulated Amiodarone to the Epicardium Reduces Atrial Fibrillation.

PubMed

Garcia, Jose R; Campbell, Peter F; Kumar, Gautam; Langberg, Jonathan J; Cesar, Liliana; Deppen, Juline N; Shin, Eric Y; Bhatia, Neal K; Wang, Lanfang; Xu, Kai; Schneider, Frank; Robinson, Brian; García, Andrés J; Levit, Rebecca D

2018-05-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although treatment options for AF exist, many patients cannot be maintained in normal sinus rhythm. Amiodarone is an effective medication for AF but has limited clinical utility because of off-target tissue toxicity. Here, we use a pig model of AF to test the efficacy of an amiodarone-containing polyethylene glycol-based hydrogel. The gel is placed directly on the atrial epicardium through the pericardial space in a minimally invasive procedure using a specially designed catheter. Implantation of amiodarone-containing gel significantly reduced the duration of sustained AF at 21 and 28 days; inducibility of AF was reduced 14 and 21 days post-delivery. Off-target organ drug levels in the liver, lungs, thyroid, and fat were significantly reduced in animals treated with epicardial amiodarone gel compared with systemic controls in small-animal distribution studies. The pericardium is an underutilized therapeutic site and may be a new treatment strategy for AF and other cardiovascular diseases. © 2018 American Heart Association, Inc.

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

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.

Influence of protein formulation and carrier solution on asymmetrical flow field-flow fractionation: a case study of the plant-produced recombinant anthrax protective antigen pp-PA83.

PubMed

Palais, Caroline; Chichester, Jessica A; Manceva, Slobodanka; Yusibov, Vidadi; Arvinte, Tudor

2015-02-01

Asymmetrical flow field-flow fractionation (afFFF) was used to investigate the properties of a plant-produced anthrax toxin protective antigen, pp-PA83. The afFFF fractogram consisted of two main peaks with molar masses similar to the molecular mass of pp-PA83 monomer. afFFF carrier solutions strongly influenced the ratio and the intensity of the two main peaks. These differences indicate that conformation changes in the pp-PA83 molecule occurred during the afFFF analysis. Similar fractograms were obtained for different pp-PA83 formulations when the afFFF carrier solution and the protein formulation were the same (or very similar). The data show that in specific cases, afFFF could be used to study protein conformation and document the importance of studying the influence of the carrier solution on afFFF. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Molecular Recognition of Methyl α-d-Mannopyranoside by Antifreeze (Glyco)Proteins

PubMed Central

2015-01-01

Antifreeze proteins and glycoproteins [AF(G)Ps] have been well-known for more than three decades for their ability to inhibit the growth and recrystallization of ice through binding to specific ice crystal faces, and they show remarkable structural compatibility with specific ice crystal faces. Here, we show that the crystal growth faces of methyl α-d-mannopyranoside (MDM), a representative pyranose sugar, also show noteworthy structural compatibility with the known periodicities of AF(G)Ps. We selected fish AFGPs (AFGP8, AFGP1–5), and a beetle AFP (DAFP1) with increasing antifreeze activity as potential additives for controlling MDM crystal growth. Similar to their effects on ice growth, the AF(G)Ps can inhibit MDM crystal growth and recrystallization, and more significantly, the effectiveness for the AF(G)Ps are well correlated with their antifreeze activity. MDM crystals grown in the presence of AF(G)Ps are smaller and have better defined shapes and are of higher quality as indicated by single crystal X-ray diffraction and polarized microscopy than control crystals, but no new polymorphs of MDM were identified by single crystal X-ray diffraction, solid-state NMR, and attenuated total reflectance infrared spectroscopy. The observed changes in the average sizes of the MDM crystals can be related to the changes in the number of the MDM nuclei in the presence of the AF(G)Ps. The critical free energy change differences of the MDM nucleation in the absence and presence of the additives were calculated. These values are close to those of the ice nucleation in the presence of AF(G)Ps suggesting similar interactions are involved in the molecular recognition of MDM by the AF(G)Ps. To our knowledge this is the first report where AF(G)Ps have been used to control crystal growth of carbohydrates and on AFGPs controlling non-ice-like crystals. Our finding suggests MDM might be a possible alternative to ice for studying the detailed mechanism of AF(G)P–crystal interactions. The relationships between AF(G)Ps and carbohydrate binding proteins are also discussed. The structural compatibility between AF(G)Ps and growing crystal faces demonstrated herein adds to the repertoire of molecular recognition by AF(G)Ps, which may have potential applications in the sugar, food, pharmaceutical, and materials industries. PMID:24918258

"Atomic, Molecular and Optical Physics Inside"

NASA Astrophysics Data System (ADS)

Garscadden, Alan

2002-05-01

I was fortunate to enjoy the advice of K. G. Emeleus during my graduate studies and for many years afterwards. He introduced me to the papers of Will Allis and later I was privileged to correspond with him. At this time I had moved from the Queens university environment to work at a large Air Force base. A personal overview is presented on the many roles that atomic, molecular and optical physics, including gaseous electronics, play in programs of the AFRL and subsequently on AF systems and operations. AFRL is not only a laboratory; it is also a defense contracting and evaluation agency. The AF sponsors basic research for several reasons:- to have an educated populace and a highly qualified work force for the nation; to enhance the technology options available to the commerce of the nation; to advance national prestige and to provide the Air Force with the best technical capabilities. The organization of AF science and technology starts with the AFOSR as the single manager of AF basic research, (6.1) funded at approximately 221M per year of which more than 70there are the Exploratory Development programs (6.2 at 695M annually) managed by AFRL where concepts are evaluated and components are developed. These programs involve industry and many universities, especially in cooperation with companies. Some of these programs that succeed transition into advanced development (6.3 at $465M annually) where integration occurs to provide a subsystem or system. While there have been misses, overall there have been many successes with impacts that provide more effective systems as recent experiences have demonstrated. The R process and planning are quite involved with Darwinian competitions for resources which then impact the research initiatives, to which principal investigators are requested to respond. Some example studies, involving primarily electron collisions, lasers, flows and combustion physics, successful and unsuccessful, are discussed.

Discriminating Talent Identified Junior Australian Footballers Using a Fundamental Gross Athletic Movement Assessment.

PubMed

Woods, Carl T; Banyard, Harry G; McKeown, Ian; Fransen, Job; Robertson, Sam

2016-09-01

Talent identification (TID) is a pertinent component of the sports sciences, affording practitioners the opportunity to target developmental interventions to a select few; optimising financial investments. However, TID is multi-componential, requiring the recognition of immediate and prospective performance. The measurement of athletic movement skill may afford practitioners insight into the latter component given its augmented relationship with functional sport specific qualities. It is currently unknown whether athletic movement skill is a discriminant quality in junior Australian football (AF). This study aimed to discriminate talent identified junior AF players from their non-talent identified counterparts using a fundamental gross athletic movement assessment. From a total of 50 under 18 (U18) AF players; two groups were classified a priori based on selection level; talent identified (n = 25; state academy representatives) and non-talent identified (n = 25; state-based competition representatives). Players performed a fundamental gross athletic movement assessment based on the Athletic Ability Assessment (AAA), consisting of an overhead squat, double lunge (left and right legs), single leg Romanian deadlift (left and right legs), and a push up (six movement criterions). Movements were scored across three assessment points using a three-point scale (resulting in a possible score of nine for each movement). A multivariate analysis of variance revealed significant between group effects on four of the six movement criterions (d = 0.56 - 0.87; p = 0.01 - 0.02). Binary logistic regression models and a receiver operating characteristic curve inspection revealed that the overhead squat score provided the greatest group discrimination (β(SE) = -0.89(0.44); p < 0.05), with a score of 4.5 classifying 64% and 88% of the talent identified and non-talent identified groups, respectively. Results support the integration of this assessment into contemporary talent identification approaches in junior AF, as it may provide coaches with insight into a juniors developmental potential.

Randomised clinical trial of cryoballoon versus irrigated radio frequency catheter ablation for atrial fibrillation-the effect of double short versus standard exposure cryoablation duration during pulmonary vein isolation (CIRCA-DOSE): methods and rationale.

PubMed

Andrade, Jason G; Deyell, Marc W; Badra, Mariano; Champagne, Jean; Dubuc, Marc; Leong-Sit, Peter; Macle, Laurent; Novak, Paul; Roux, Jean-Francois; Sapp, John; Tang, Anthony; Verma, Atul; Wells, George A; Khairy, Paul

2017-10-05

Pulmonary vein isolation (PVI) is an effective therapy for paroxysmal atrial fibrillation (AF), but it has limitations. The two most significant recent advances have centred on the integration of real-time quantitative assessment of catheter contact force into focal radio frequency (RF) ablation catheters and the development of dedicated ablation tools capable of achieving PVI with a single ablation lesion (Arctic Front cryoballoon, Medtronic, Minneapolis, MN, USA). Although each of these holds promise for improving the clinical success of catheter ablation of AF, there has not been a rigorous comparison of these advanced ablation technologies. Moreover, the optimal duration of cryoablation (freezing time) has not been determined. Patients undergoing an initial PVI procedure for paroxysmal AF will be recruited. Patients will be randomised 1:1:1 between contact-force irrigated RF ablation, short duration cryoballoon ablation (2 min applications) and standard duration cryoballoon ablation (4 min applications). The primary outcome is time to first documented AF recurrence on implantable loop recorder. With a sample size of 111 per group and a two-sided 0.025 significance level (to account for the two main comparisons), the study will have 80% power (using a log-rank test) to detect a difference of 20% between contact force RF catheter ablation and either of the two cryoballoon ablation groups. Factoring in a 4% loss to follow-up, 116 patients per group should be randomised and followed for a year (total study population of 348). The study was approved by the University of British Columbia Office of Research (Services) Ethics Clinical Research Ethics Board. Results of the study will be submitted for publication in a peer-reviewed journal. NCT01913522; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Temporal Variation and Association of Aflatoxin B1 Albumin-Adduct Levels with Socio-Economic and Food Consumption Factors in HIV Positive Adults

PubMed Central

Jolly, Pauline E.; Akinyemiju, Tomi F.; Jha, Megha; Aban, Inmaculada; Gonzalez-Falero, Andrea; Joseph, Dnika

2015-01-01

The association between aflatoxin exposure and alteration in immune responses observed in humans suggest that aflatoxin could suppress the immune system and work synergistically with HIV to increase disease severity and progression to AIDS. No longitudinal study has been conducted to assess exposure to aflatoxin (AF) among HIV positive individuals. We examined temporal variation in AFB1 albumin adducts (AF-ALB) in HIV positive Ghanaians, and assessed the association with socioeconomic and food consumption factors. We collected socioeconomic and food consumption data for 307 HIV positive antiretroviral naive adults and examined AF-ALB levels at recruitment (baseline) and at six (follow-up 1) and 12 (follow-up 2) months post-recruitment, by age, gender, socioeconomic status (SES) and food consumption patterns. Generalized linear models were used to examine the influence of socioeconomic and food consumption factors on changes in AF-ALB levels over the study period, adjusting for other covariates. AF-ALB levels (pg/mg albumin) were lower at baseline (mean AF-ALB: 14.9, SD: 15.9), higher at six months (mean AF-ALB: 23.3, SD: 26.6), and lower at 12 months (mean AF-ALB: 15.3, SD: 15.4). Participants with the lowest SES had the highest AF-ALB levels at baseline and follow up-2 compared with those with higher SES. Participants who bought less than 20% of their food and who stored maize for less than two months had lower AF-ALB levels. In the adjusted models, there was a statistically significant association between follow up time and season (dry or rainy season) on AF-ALB levels over time (p = 0.04). Asymptomatic HIV-positive Ghanaians had high plasma AF-ALB levels that varied according to season, socioeconomic status, and food consumption patterns. Steps need to be taken to ensure the safety and security of the food supply for the population, but in particular for the most vulnerable groups such as HIV positive people. PMID:26633502

Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.

PubMed

Slavik, R S; Tisdale, J E; Borzak, S

2001-01-01

This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method. Larger, well-designed randomized controlled trials with clinically important endpoints in specific populations of AF patients are needed. Copyright 2001 by W.B. Saunders Company

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 Association, Inc., by Wiley Blackwell.

Effect of pulmonary vein isolation on the left-to-right atrial dominant frequency gradient in human atrial fibrillation.

PubMed

Lazar, Sorin; Dixit, Sanjay; Callans, David J; Lin, David; Marchlinski, Francis E; Gerstenfeld, Edward P

2006-08-01

We previously demonstrated the existence of a left-to-right atrial dominant frequency gradient during paroxysmal but not persistent atrial fibrillation (AF) in humans. One possible mechanism of the left-to-right dominant frequency gradient involves the role of the pulmonary veins (PVs) in AF maintenance. The purpose of this study was to examine the effect of PV isolation on the dominant frequency gradient and outcome after PV isolation. Patients with either paroxysmal or persistent AF were studied. Recordings were made from catheters in the coronary sinus (CS), posterior right atrium (RA), and posterior left atrium (LA) during AF before and after PV isolation. Mean left-to-right dominant frequency gradient was measured before and after segmental PV isolation. Patients were followed for AF recurrence after PV isolation. Twenty-seven patients with paroxysmal (n = 15) or persistent (n = 12) AF were studied. In the paroxysmal group, baseline dominant frequency was greatest in the posterior LA with a significant left-to-right atrial dominant frequency gradient (posterior LA = 6.2 +/- 0.9 Hz, CS = 5.8 +/- 0.8 Hz, posterior RA = 5.4 +/- 0.9 Hz; P <.001). After PV isolation, there was no regional difference in dominant frequency (5.9 +/- 0.7 Hz vs 5.7 +/- 0.6 Hz vs 5.7 +/- 0.7 Hz, respectively; P = NS). In the persistent AF group, there was no overall difference in dominant frequency among sites before or after PV isolation (P = NS); however, patients with long-term freedom from AF after PV isolation had a higher left-to-right dominant frequency gradient compared with patients with recurrent AF (0.4 vs 0.1 Hz; P <.05). PV isolation results in a loss in the left-to-right dominant frequency gradient in patients with paroxysmal AF. This finding supports the critical role of PVs in the maintenance of ongoing paroxysmal AF. Patients with persistent AF and a baseline left-to-right dominant frequency gradient have a better success rate with PV isolation alone compared with patients without a dominant frequency gradient.

Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.

PubMed

Mulligan, Jennifer K; Pasquini, Whitney N; Carroll, William W; Williamson, Tucker; Reaves, Nicholas; Patel, Kunal J; Mappus, Elliott; Schlosser, Rodney J; Atkinson, Carl

2017-01-01

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Agroforestry systems of the lowland alluvial valleys of the Tehuacán-Cuicatlán Biosphere Reserve: an evaluation of their biocultural capacity.

PubMed

Vallejo, Mariana; Casas, Alejandro; Pérez-Negrón, Edgar; Moreno-Calles, Ana I; Hernández-Ordoñez, Omar; Tellez, Oswaldo; Dávila, Patricia

2015-02-19

Agroforestry systems (AFS) are valuable production systems that allow concealing benefits provision with conservation of biodiversity and ecosystem services. We analysed AFS of the zone of alluvial valleys of the Tehuacán-Cuicatlán Valley (TCV), Mexico, the most intensive agricultural systems within a region recognized for harbouring one of the most ancient agricultural experience of the New World. We hypothesized that the biodiversity conservation capacity of AFS would be directly related to traditional agricultural features and inversely related to management intensity. Agricultural practices, use frequency of machinery and chemical inputs, and proportion of forest and cultivated areas were described in 15 AFS plots in alluvial valleys of the Salado River in three villages of the region. With the information, we constructed a management intensity index and compared among plots and villages. We documented the reasons why people maintain wild plant species and traditional practices. Perennial plant species were sampled in vegetation of AFS (15 plots) and unmanaged forests (12 plots 500 m(2)) in order to compare richness, diversity and other ecological indicators in AFS and forest. In all studied sites, people combine traditional and intensive agricultural practices. Main agroforestry practices are ground terraces and borders surrounding AFS plots where people maintain vegetation. According to people, the reasons for maintaining shrubs and trees in AFS were in order of importance are: Beauty and shade provision (14% of people), fruit provision (7%), protection against strong wind, and favouring water and soil retention. We recorded 66 species of trees and shrubs in the AFS studied, 81% of them being native species that represent 38% of the perennial plant species recorded in forests sampled. Land tenure and institutions vary among sites but not influenced the actions for maintaining the vegetation cover in AFS. Plant diversity decreased with increasing agricultural intensity. Maintenance of vegetation cover did not confront markedly with the intensive agricultural practices. It is possible the expansion and enrichment of vegetation in terraces and borders of AFS. Information available on plant species and local techniques is potentially useful for a regional program of biodiversity conservation considering AFS as keystones.

Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count Tests: A Comprehensive Systematic Review with Meta-Analysis

PubMed Central

Weymann, Alexander; Ali-Hasan-Al-Saegh, Sadeq; Sabashnikov, Anton; Popov, Aron-Frederik; Mirhosseini, Seyed Jalil; Liu, Tong; Lotfaliani, Mohammadreza; de Oliveira Sá, Michel Pompeu Barros; Baker, William L.; Yavuz, Senol; Zeriouh, Mohamed; Jang, Jae-Sik; Dehghan, Hamidreza; Meng, Lei; Testa, Luca; D’Ascenzo, Fabrizio; Benedetto, Umberto; Tse, Gary; Nombela-Franco, Luis; Dohmen, Pascal M.; Deshmukh, Abhishek J.; Linde, Cecilia; Biondi-Zoccai, Giuseppe; Stone, Gregg W.; Calkins, Hugh

2017-01-01

Background Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and is routinely used in the workup of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of hematological parameters in the CBC test with new-onset and recurrent AF. Material/Methods We conducted a meta-analysis of observational studies evaluating hematologic parameters in patients with new-onset AF and recurrent AF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. Results The literature search of all major databases retrieved 2150 studies. After screening, 70 studies were analyzed in the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of −26.39×109/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001), white blood cell (WBC) (WMD=−0.005×109/L and p=0.83), neutrophil to lymphocyte ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW) (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF revealed PC (WMD=−2.71×109/L and p=0.59), WBC (WMD=0.20×109/L (95% CI: 0.08 to 0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001). Conclusions Hematological parameters have significant ability to predict occurrence and recurrence of AF. Therefore, emphasizing the potential predictive role of hematological parameters for new-onset and recurrent AF, we recommend adding the CBC test to the diagnostic modalities of AF in clinical practice. PMID:28496093

Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count Tests: A Comprehensive Systematic Review with Meta-Analysis.

PubMed

Weymann, Alexander; Ali-Hasan-Al-Saegh, Sadeq; Sabashnikov, Anton; Popov, Aron-Frederik; Mirhosseini, Seyed Jalil; Liu, Tong; Lotfaliani, Mohammadreza; Sá, Michel Pompeu Barros de Oliveira; Baker, William L L; Yavuz, Senol; Zeriouh, Mohamed; Jang, Jae-Sik; Dehghan, Hamidreza; Meng, Lei; Testa, Luca; D'Ascenzo, Fabrizio; Benedetto, Umberto; Tse, Gary; Nombela-Franco, Luis; Dohmen, Pascal M; Deshmukh, Abhishek J; Linde, Cecilia; Biondi-Zoccai, Giuseppe; Stone, Gregg W; Calkins, Hugh; Surgery And Cardiology-Group Imcsc-Group, Integrated Meta-Analysis Of Cardiac

2017-05-12

BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and is routinely used in the workup of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of hematological parameters in the CBC test with new-onset and recurrent AF. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating hematologic parameters in patients with new-onset AF and recurrent AF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS The literature search of all major databases retrieved 2150 studies. After screening, 70 studies were analyzed in the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of -26.39×10^9/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001), white blood cell (WBC) (WMD=-0.005×10^9/L and p=0.83), neutrophil to lymphocyte ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW) (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF revealed PC (WMD=-2.71×109/L and p=0.59), WBC (WMD=0.20×10^9/L (95% CI: 0.08 to 0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001). CONCLUSIONS Hematological parameters have significant ability to predict occurrence and recurrence of AF. Therefore, emphasizing the potential predictive role of hematological parameters for new-onset and recurrent AF, we recommend adding the CBC test to the diagnostic modalities of AF in clinical practice.

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%.

Thermophilic Ferritin: Versatile Nanohost

NASA Astrophysics Data System (ADS)

Pulsipher, Katherine W.

Thermophilic ferritin from Archaeoglobus fulgidus (AfFtn) is a 24meric, hollow, cage-like protein, whose native function is the oxidation, mineralization, and storage of iron. Unique among ferritins, its self-assembly is dependent on high ionic strength, reflecting the deep sea thermal vent environment where A. fulgidus is found. This ionic strength dependence can be used to encapsulate charged cargo within the AfFtn cavity. Its subunits self-assemble into tetrahedral symmetry, resulting in four, large (4.5 nm), triangular pores, not found in other ferritins. Due to its size (12 nm outer diameter, 8 nm inner diameter), self-assembly properties, and potential for both genetic and chemical modification, AfFtn is an ideal nanocontainer for a variety of cargo, including inorganic nanoparticles and proteins. We have sought to better understand the self-assembly of AfFtn and its encapsulation of various cargo. Guided by computational analysis and through mutagenesis, we have investigated the role of electrostatics along the AfFtn trimeric interface in self-assembly. We have developed a series of single point mutants with increasingly favorable cage assembly. One specific mutation, E65R, has a dramatic effect on AfFtn, almost entirely preventing disassembly and enhancing thermal stability by 14°C. By using a novel graphene-based microelectrode, we have determined that AfFtn maintains its quaternary structure upon encapsulation of a gold nanoparticle, developing a new tool for investigating protein-nanomaterial interactions. We have also shown that AfFtn can be used to template seeded gold nanoparticle growth and have explored two often neglected factors in ferritin-nanoparticle templating: the charge of the gold salt used, and the size of the protein pores. Our results demonstrate that the open, porous structure of AfFtn allows more efficient particle growth than typical closed-pore ferritins. Finally, we have expanded the cargo uptake of AfFtn beyond nanoparticles to include proteins, encapsulating supercharged GFP. The AfFtn-cargo complexes developed here have application in catalysis, nanomaterials synthesis, and targeted delivery.

Rationale and design of a prospective study of the clinical significance of atrial arrhythmias detected by implanted device diagnostics: the TRENDS study.

PubMed

Glotzer, Taya V; Daoud, Emile G; Wyse, D George; Singer, Daniel E; Holbrook, Reece; Pruett, Khadeeja; Smith, Kenneth; Hilker, Christopher E

2006-01-01

Sustained atrial fibrillation (AF) is a common risk factor for stroke. While intermittent AF also appears to pose a substantial stroke risk, the quantitative relationship between the percentage of time spent in AF and stroke risk is poorly specified and "intermittent" AF is not the same as paroxysmal AF. Improved assessment of the impact of AF burden on stroke risk will allow more targeted and safer use of antithrombotic therapy. The primary objective of this study is to determine if AT/AF (all device detected atrial tachyarrhythmias, including atrial flutter, atrial fibrillation, and atrial tachycardia) burden over a 30 day period is an independent predictor of the occurrence of ischemic stroke, transient ischemic attack (TIA) and/or systemic embolism in subjects not receiving anticoagulation therapy. TRENDS is a prospective, post-market, non-randomized, multicenter study designed to enroll 3100 subjects who have an independent Class I/II indication for cardiac rhythm device implantation and who have demographic features suggestive of an increased risk for thromboembolic complications related to AT/AF. All implanted devices will have the ability to collect long-term AT/AF burden trending data and will be equivalently programmed to ensure consistent data collection. All subjects will be followed with device interrogations every 3 months and clinic visits every 6 months for 1 year. Subjects with a documented history of AT/AF prior to enrollment and those who develop AT/AF during the 12-month follow-up will be followed until the last subject enrolled in the study has completed their 24-month follow-up. The results of the TRENDS study should help clarify the implications of data retrieved from an implantable device with regard to the risk for thromboembolic complications from atrial arrhythmias, even in the absence of symptoms.

Lean body mass and risk of incident atrial fibrillation in post-menopausal women.

PubMed

Azarbal, Farnaz; Stefanick, Marcia L; Assimes, Themistocles L; Manson, JoAnn E; Bea, Jennifer W; Li, Wenjun; Hlatky, Mark A; Larson, Joseph C; LeBlanc, Erin S; Albert, Christine M; Nassir, Rami; Martin, Lisa W; Perez, Marco V

2016-05-21

High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Complementary DNA cloning, sequence analysis, and tissue transcription profile of a novel U2AF2 gene from the Chinese Banna mini-pig inbred line.

PubMed

Wang, S Y; Huo, J L; Miao, Y W; Cheng, W M; Zeng, Y Z

2013-04-02

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an important gene for pre-messenger RNA splicing in higher eukaryotes. In this study, the Banna mini-pig inbred line (BMI) U2AF2 coding sequence (CDS) was cloned, sequenced, and characterized. The U2AF2 complete CDS was amplified using the reverse transcription-polymerase chain reaction (RT-PCR) technique based on the conserved sequence information of cattle and known highly homologous swine expressed sequence tags. This novel gene was deposited into the National Center for Biotechnology Information database (Accession No. JQ839267). Sequence analysis revealed that the BMI U2AF2 coding sequence consisted of 1416 bp and encoded 471 amino acids with a molecular weight of 53.12 kDa. The protein sequence has high sequence homology with U2AF65 of 6 species - Homo sapiens (100%), Equus caballus (100%), Canis lupus (100%), Macaca mulatta (99.8%), Bos taurus (74.4%), and Mus musculus (74.4%). The phylogenetic tree analysis revealed that BMI U2AF65 has a closer genetic relationship with B. taurus U2AF65 than with U2AF65 of E. caballus, C. lupus, M. mulatta, H. sapiens, and M. musculus. RT-PCR analysis showed that BMI U2AF2 was most highly expressed in the brain; moderately expressed in the spleen, lung, muscle, and skin; and weakly expressed in the liver, kidney, and ovary. Its expression was nearly silent in the spinal cord, nerve fiber, heart, stomach, pancreas, and intestine. Three microRNA target sites were predicted in the CDS of BMI U2AF2 messenger RNA. Our results establish a foundation for further insight into this swine gene.

Characterization of Genome-Wide Association-Identified Variants for Atrial Fibrillation in African Americans

PubMed Central

Delaney, Jessica T.; Jeff, Janina M.; Brown, Nancy J.; Pretorius, Mias; Okafor, Henry E.; Darbar, Dawood; Roden, Dan M.; Crawford, Dana C.

2012-01-01

Background Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown. Methodology/Principal Findings We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r2<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13–0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59–7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46–45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls. Conclusions/Significance Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations. PMID:22384221

Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria

PubMed Central

Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

2013-01-01

Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche–Ramirez–Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca2+ handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re-entrant excitation waves. PMID:23732649

Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.

PubMed

Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

2013-09-01

Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca(2+) handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re-entrant excitation waves.

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.

Albiflorin ameliorates obesity by inducing thermogenic genes via AMPK and PI3K/AKT in vivo and in vitro.

PubMed

Jeong, Mi-Young; Park, Jinbong; Youn, Dong-Hyun; Jung, Yunu; Kang, JongWook; Lim, Seona; Kang, Min-Woo; Kim, Hye-Lin; So, Hong-Seob; Park, Raekil; Hong, Seung-Heon; Um, Jae-Young

2017-08-01

Brown adipose tissue (BAT) activation has been identified as a possible target to treat obesity and to protect against metabolic diseases by increasing energy consumption. We explored whether albiflorin (AF), a natural compound, could contribute to lowering the high risk of obesity with BAT and primary brown preadipocytes in vivo and in vitro. Human adipose tissue-derived mesenchymal stem cells (hAMSCs) were cultured with adipogenic differentiation media with or without AF. Male C57BL/6J mice (n=5 per group) were fed a high-fat diet (HFD) for six weeks with or without AF. Brown preadipocytes from the interscapular BAT of mice were cultured with or without AF. In white adipogenic differentiation of hAMSCs, AF treatment significantly reduced the formation of lipid droplets and the expression of adipogenesis-related genes. In HFD-induced obese C57BL/6J mice, AF treatment significantly reduced body weight gain as well as the weights of the white adipose tissue, liver and spleen. Furthermore, AF induced the expression of genes involved in thermogenic function in BAT. In primary brown adipocytes, AF effectively stimulated the expressions of thermogenic genes and markedly up-regulated the AMP-activated protein kinase (AMPK) signaling pathway. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 nullified the induction of the thermogenic genes by AF in primary brown adipocytes. Moreover, AF activated beige cell marker genes induced by the pharmacological activation of peroxisome proliferator-activated receptor γ in hAMSCs. This study shows that AF prevents the development of obesity in hAMSCs and mice fed an HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes by AMPK and PI3K/AKT. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Medication therapy disease management: Geisinger's approach to population health management.

PubMed

Jones, Laney K; Greskovic, Gerard; Grassi, Dante M; Graham, Jove; Sun, Haiyan; Gionfriddo, Michael R; Murray, Michael F; Manickam, Kandamurugu; Nathanson, Douglas C; Wright, Eric A; Evans, Michael A

2017-09-15

Pharmacists' involvement in a population health initiative focused on chronic disease management is described. Geisinger Health System has cultivated a culture of innovation in population health management, as highlighted by its ambulatory care pharmacy program, the Medication Therapy Disease Management (MTDM) program. Initiated in 1996, the MTDM program leverages pharmacists' pharmacotherapy expertise to optimize care and improve outcomes. MTDM program pharmacists are trained and credentialed to manage over 16 conditions, including atrial fibrillation (AF) and multiple sclerosis (MS). Over a 15-year period, Geisinger Health Plan (GHP)-insured patients with AF whose warfarin therapy was managed by the MTDM program had, on average, 18% fewer emergency department (ED) visits and 18% fewer hospitalizations per year than GHP enrollees with AF who did not receive MTDM services, with 23% lower annual total care costs. Over a 2-year period, GHP-insured patients with MS whose pharmacotherapy was managed by pharmacists averaged 28% fewer annual ED visits than non-pharmacist-managed patients; however, the mean annual total care cost was 21% higher among MTDM clinic patients. The Geisinger MTDM program has evolved over 20 years from a single pharmacist-run anticoagulation clinic into a large program focused on managing the health of an ever-growing population. Initial challenges in integrating pharmacists into the Geisinger patient care framework as clinical experts were overcome by demonstrating the MTDM program's positive impact on patient outcomes. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier

PubMed Central

Santos, Margarida A.; Faryabi, Robert B.; Ergen, Aysegul V.; Day, Amanda M.; Malhowski, Amy; Canela, Andres; Onozawa, Masahiro; Lee, Ji-Eun; Callen, Elsa; Gutierrez-Martinez, Paula; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Deshpande, Aniruddha; Sharrow, Susan; Rossi, Derrick J.; Ito, Keisuke; Ge, Kai; Aplan, Peter D.; Armstrong, Scott A.; Nussenzweig, André

2015-01-01

Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells1. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks2–4, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma5,6, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL–AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4−/− MLL–AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL–AF9 blasts, which requires cyclin-dependent kinase inhibitor p21Cip1 (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia. PMID:25079327

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

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.

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.

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

Intraretinal Correlates of Reticular Pseudodrusen Revealed by Autofluorescence and En Face OCT.

PubMed

Paavo, Maarjaliis; Lee, Winston; Merriam, John; Bearelly, Srilaxmi; Tsang, Stephen; Chang, Stanley; Sparrow, Janet R

2017-09-01

We sought to determine whether information revealed from the reflectance, autofluorescence, and absorption properties of RPE cells situated posterior to reticular pseudodrusen (RPD) could provide insight into the origins and structure of RPD. RPD were studied qualitatively by near-infrared fundus autofluorescence (NIR-AF), short-wavelength fundus autofluorescence (SW-AF), and infrared reflectance (IR-R) images, and the presentation was compared to horizontal and en face spectral domain optical coherence tomographic (SD-OCT) images. Images were acquired from 23 patients (39 eyes) diagnosed with RPD (mean age 80.7 ± 7.1 [SD]; 16 female; 4 Hispanics, 19 non-Hispanic whites). In SW-AF, NIR-AF, and IR-R images, fundus RPD were recognized as interlacing networks of small scale variations in IR-R and fluorescence (SW-AF, NIR-AF) intensities. Darkened foci of RPD colocalized in SW-AF and NIR-AF images, and in SD-OCT images corresponded to disturbances of the interdigitation (IZ) and ellipsoid (EZ) zones and to more pronounced hyperreflective lesions traversing photoreceptor-attributable bands in SD-OCT images. Qualitative assessment of the outer nuclear layer (ONL) revealed thinning as RPD extended radially from the outer to inner retina. In en face OCT, hyperreflective areas in the EZ band correlated topographically with hyporeflective foci at the level of the RPE. The hyperreflective lesions corresponding to RPD in SD-OCT scans are likely indicative of degenerating photoreceptor cells. The darkened foci at positions of RPD in NIR-AF and en face OCT images indicate changes in the RPE monolayer with the reduced NIR-AF and en face OCT signal suggesting a reduction in melanin that could be accounted for by RPE thinning.

The cost savings of newer oral anticoagulants in atrial fibrillation-related stroke prevention
.

PubMed

Masbah, Norliana; Macleod, Mary Joan

2017-03-01

Newer oral anticoagulants (NOACs) are considered as better alternatives compared to warfarin for stroke prevention in atrial fibrillation (AF) in terms of clinical effectiveness although the drug acquisition cost is more substantial. This study determined the direct stroke costs based on inpatient hospitalization in a subgroup of the National Health Service (NHS) Grampian, Scotland, stroke patients, to evaluate the differences in costs related to AF stroke, and to ascertain whether the use of NOACs within this study population would produce greater cost savings. Hospitalization records over 5 years involving 3,601 stroke patients were analyzed. Direct costs were based on the costs of inpatient length of stay per day. The potential cost savings if AF patients had been on NOACs were estimated using efficacy data from a landmark clinical trial involving rivaroxaban. Out of the total stroke cases, 29.5% of total stroke cases were secondary to AF, and these cases were more severe with longer hospitalizations. Only 254 patients (39.4%) with confirmed AF were anticoagulated with warfarin prior to admission. AF patients incurred higher median costs (£4,719 (interquartile range (IQR) £1,815 - £12,452) compared to non-AF patients (£3,267 (IQR £1,175 - £11,368)), although the association was statistically insignificant. The use of NOACs in AF-related patients with ischemic strokes would potentially prevent more strokes (leading to 58 fewer cases in comparison to warfarin), resulting in 17.1% in total cost reduction. AF stroke patients incurred higher total direct costs compared to non-AF cases. However, more cost savings were evident with NOACs, due to more strokes being prevented through the use of NOACs compared to warfarin.
.

Impact of high-grade Atrioventricular block and cumulative frequent pacing on atrial arrhythmias.

PubMed

Wali, Eisha; Deshmukh, Amrish; Bukari, Abdallah; Broman, Michael; Aziz, Zaid; Beaser, Andrew; Upadhyay, Gaurav; Nayak, Hemal M; Tung, Roderick; Ozcan, Cevher

2018-06-21

The relationship between high-grade AV block (HGAVB) with cumulative frequent pacing and risk of atrial arrhythmias (AAs) has not been well characterized. We hypothesized HGAVB and pacing may have significant impact on incidence and prevalence of AAs by modulating atrial substrate. To determine impact of HGAVB and pacing on AAs including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). All consecutive patients who underwent dual chamber pacemaker implantation for HGAVB from 2005 to 2011 at the University of Chicago were included. AAs and percent of pacing were detected through device interrogation. Patients' data were collected from electronic medical records and clinic visits. A total of 166 patients (mean age 71±15 years; 54% female, 56% African-American) were studied. AF was documented in 27% of patients before pacemaker implantation. During a mean 5.8±2.2 years of follow-up, 47% had device-detected AF, 10% AFL and 26% AT. New-onset AF was documented in 40 of the 122 patients without prior AF (33%). Continuous (≥99%) right ventricular pacing was associated with significantly decreased AF prevalence (34% versus 59%, p = 0.005), and correlated with lower incidence (26% versus 41%, p = 0.22). Pacing suppressed AF in 14% of patients with baseline AF; those patients had lower atrial pacing (3.2% versus 45%, p < 0.0001). Left atrial dilation was the only independent predictor of AF with frequent pacing (p = 0.009). HGAVB is associated with high incidence and prevalence of AAs with and without pacing. Cumulative frequent (≥99%) ventricular pacing reduces risk of AF in patients with HGAVB. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Atrial Fibrillation Screening in Nonmetropolitan Areas Using a Telehealth Surveillance System With an Embedded Cloud-Computing Algorithm: Prospective Pilot Study.

PubMed

Chen, Ying-Hsien; Hung, Chi-Sheng; Huang, Ching-Chang; Hung, Yu-Chien; Hwang, Juey-Jen; Ho, Yi-Lwun

2017-09-26

Atrial fibrillation (AF) is a common form of arrhythmia that is associated with increased risk of stroke and mortality. Detecting AF before the first complication occurs is a recognized priority. No previous studies have examined the feasibility of undertaking AF screening using a telehealth surveillance system with an embedded cloud-computing algorithm; we address this issue in this study. The objective of this study was to evaluate the feasibility of AF screening in nonmetropolitan areas using a telehealth surveillance system with an embedded cloud-computing algorithm. We conducted a prospective AF screening study in a nonmetropolitan area using a single-lead electrocardiogram (ECG) recorder. All ECG measurements were reviewed on the telehealth surveillance system and interpreted by the cloud-computing algorithm and a cardiologist. The process of AF screening was evaluated with a satisfaction questionnaire. Between March 11, 2016 and August 31, 2016, 967 ECGs were recorded from 922 residents in nonmetropolitan areas. A total of 22 (2.4%, 22/922) residents with AF were identified by the physician's ECG interpretation, and only 0.2% (2/967) of ECGs contained significant artifacts. The novel cloud-computing algorithm for AF detection had a sensitivity of 95.5% (95% CI 77.2%-99.9%) and specificity of 97.7% (95% CI 96.5%-98.5%). The overall satisfaction score for the process of AF screening was 92.1%. AF screening in nonmetropolitan areas using a telehealth surveillance system with an embedded cloud-computing algorithm is feasible. ©Ying-Hsien Chen, Chi-Sheng Hung, Ching-Chang Huang, Yu-Chien Hung, Juey-Jen Hwang, Yi-Lwun Ho. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 26.09.2017.

Identification of Rare Variants in TNNI3 with Atrial Fibrillation in a Chinese GeneID Population

PubMed Central

Wang, Chuchu; Wu, Manman; Qian, Jin; Li, Bin; Tu, Xin; Xu, Chengqi; Li, Sisi; Chen, Shanshan; Zhao, Yuanyuan; Huang, Yufeng; Shi, Lisong; Cheng, Xiang; Liao, Yuhua; Chen, Qiuyun; Xia, Yunlong; Yao, Wei; Wu, Gang; Cheng, Mian; Wang, Qing K.

2015-01-01

Despite advances by genome-wide association studies (GWAS), much of heritability of common human diseases remains missing, a phenomenon referred to as ‘missing heritability’. One potential cause for ‘missing heritability’ is the rare susceptibility variants overlooked by GWAS. Atrial fibrillation (AF) is the most common arrhythmia seen at hospitals and increases risk of stroke by 5-fold and doubles risk of heart failure and sudden death. Here we studied one large Chinese family with AF and hypertrophic cardiomyopathy (HCM). Whole-exome sequencing analysis identified a mutation in TNNI3, R186Q, that co-segregated with the disease in the family, but did not exist in >1,583 controls, suggesting that R186Q causes AF and HCM. High-resolution melting curve analysis and direct DNA sequence analysis were then used to screen mutations in all exons and exon-intron boundaries of TNNI3 in a panel of 1,127 unrelated AF patients and 1,583 non-AF subjects. Four novel missense variants were identified in TNNI3, including E64G, M154L, E187G and D196G in four independent AF patients, but no variant was found in 1,583 non-AF subjects. All variants were not found in public databases, including the ExAC Browser database with 60,706 exomes. These data suggests that rare TNNI3 variants are associated with AF (P=0.03). TNNI3 encodes troponin I, a key regulator of the contraction-relaxation function of cardiac muscle and was not previously implicated in AF. Thus, this study may identify a new biological pathway for the pathogenesis of AF and provides evidence to support the rare variant hypothesis for missing heritability. PMID:26169204

HATCH score in the prediction of new-onset atrial fibrillation after catheter ablation of typical atrial flutter.

PubMed

Chen, Ke; Bai, Rong; Deng, Wenning; Gao, Chuanyu; Zhang, Jing; Wang, Xianqing; Wang, Shunbao; Fu, Haixia; Zhao, Yonghui; Zhang, Jiaying; Dong, Jianzeng; Ma, Changsheng

2015-07-01

New-onset atrial fibrillation (AF) is not uncommon after ablation of typical atrial flutter (AFL); however, limited data are available for a risk prediction model for the future occurrence of AF in patients with typical AFL undergoing successful catheter ablation. This study aimed to determine whether the HATCH score (which is based on hypertension, age ≥75 years, transient ischemic attack or stroke, chronic obstructive pulmonary disease, and heart failure) is useful for risk prediction of subsequent AF after ablation of typical AFL. A total of 216 consecutive patients presenting with typical AFL and no history of AF who underwent successful catheter ablation were enrolled in the study. The clinical endpoint was occurrence of new-onset AF during follow-up after ablation. During a follow-up period of 29.1 ± 18.3 months, 85 patients (39%) experienced at least 1 episode of AF. Multivariate Cox regression analysis demonstrated that the HATCH score (hazard ratio 1.784; 95% confidence interval 1.352-2.324; P < .001) and left atrial diameter (hazard ratio 1.270; 95% confidence interval 1.115-1.426; P < .001) were independently associated with new-onset AF after typical AFL ablation. The area under the receiver operator characteristic curve based on the HATCH score for prediction of new-onset AF was 0.743. The HATCH score could be used to stratify the patients into 2 groups with different incidences of new-onset AF (69% vs 27%, P < .001) at a cutoff value of 2. The HATCH score is a useful predictor of new-onset AF after typical AFL ablation. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

First Characterization of Human Amniotic Fluid Stem Cell Extracellular Vesicles as a Powerful Paracrine Tool Endowed with Regenerative Potential.

PubMed

Balbi, Carolina; Piccoli, Martina; Barile, Lucio; Papait, Andrea; Armirotti, Andrea; Principi, Elisa; Reverberi, Daniele; Pascucci, Luisa; Becherini, Pamela; Varesio, Luigi; Mogni, Massimo; Coviello, Domenico; Bandiera, Tiziano; Pozzobon, Michela; Cancedda, Ranieri; Bollini, Sveva

2017-05-01

Human amniotic fluid stem cells (hAFS) have shown a distinct secretory profile and significant regenerative potential in several preclinical models of disease. Nevertheless, little is known about the detailed characterization of their secretome. Herein we show for the first time that hAFS actively release extracellular vesicles (EV) endowed with significant paracrine potential and regenerative effect. c-KIT + hAFS were isolated from leftover samples of amniotic fluid from prenatal screening and stimulated to enhance EV release (24 hours 20% O 2 versus 1% O 2 preconditioning). The capacity of the c-KIT + hAFS-derived EV (hAFS-EV) to induce proliferation, survival, immunomodulation, and angiogenesis were investigated in vitro and in vivo. The hAFS-EV regenerative potential was also assessed in a model of skeletal muscle atrophy (HSA-Cre, Smn F7/F7 mice), in which mouse AFS transplantation was previously shown to enhance muscle strength and survival. hAFS secreted EV ranged from 50 up to 1,000 nm in size. In vitro analysis defined their role as biological mediators of regenerative, paracrine effects while their modulatory role in decreasing skeletal muscle inflammation in vivo was shown for the first time. Hypoxic preconditioning significantly induced the enrichment of exosomes endowed with regenerative microRNAs within the hAFS-EV. In conclusion, this is the first study showing that c-KIT + hAFS dynamically release EV endowed with remarkable paracrine potential, thus representing an appealing tool for future regenerative therapy. Stem Cells Translational Medicine 2017;6:1340-1355. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Analysis of gene expression provides insights into the mechanism of cadmium tolerance in Acidithiobacillus ferrooxidans.

PubMed

Chen, Minjie; Li, Yanjun; Zhang, Li; Wang, Jianying; Zheng, Chunli; Zhang, Xuefeng

2015-02-01

Acidithiobacillus ferrooxidans plays a critical role in metal solubilization in the biomining industry, and occupies an ecological niche characterized by high acidity and high concentrations of toxic heavy metal ions. In order to investigate the possible metal resistance mechanism, the cellular distribution of cadmium was tested. The result indicated that Cd(2+) entered the cells upon initial exposure resulting in increased intracellular concentrations, followed by its excretion from the cells during subsequent growth and adaptation. Sequence homology analyses were used to identify 10 genes predicted to participate in heavy metal homeostasis, and the expression of these genes was investigated in cells cultured in the presence of increasing concentrations of toxic divalent cadmium (Cd(2+)). The results suggested that one gene (cmtR A.f ) encoded a putative Cd(2+)/Pb(2+)-responsive transcriptional regulator; four genes (czcA1 A.f , czcA2 A.f , czcB1 A.f ; and czcC1 A.f ) encoded heavy metal efflux proteins for Cd(2+); two genes (cadA1 A.f and cadB1 A.f ) encoded putative cation channel proteins related to the transport of Cd(2+). No significant enhancement of gene expression was observed at low concentrations of Cd(2+) (5 mM) and most of the putative metal resistance genes were up-regulated except cmtR A.f , cadB3 A.f ; and czcB1 A.f at higher concentrations (15 and 30 mM) according to real-time polymerase chain reaction. A model was developed for the mechanism of resistance to cadmium ions based on homology analyses of the predicted genes, the transcription of putative Cd(2+) resistance genes, and previous work.

P-wave morphology and the risk of incident ischemic stroke in the Multi-Ethnic Study of Atherosclerosis.

PubMed

Kamel, Hooman; Soliman, Elsayed Z; Heckbert, Susan R; Kronmal, Richard A; Longstreth, W T; Nazarian, Saman; Okin, Peter M

2014-09-01

Emerging data suggest that left atrial disease may cause ischemic stroke in the absence of atrial fibrillation or flutter (AF). If true, this condition may provide a cause for many strokes currently classified as cryptogenic. Among 6741 participants in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cerebrovascular or cardiovascular disease (including AF) at baseline, we examined the association between markers of left atrial abnormality on a standard 12-lead ECG-specifically P-wave area, duration, and terminal force in lead V1-and the subsequent risk of ischemic stroke while accounting for incident AF. During a median follow-up of 8.5 years, 121 participants (1.8%) had a stroke and 541 participants (8.0%) were diagnosed with AF. In Cox proportional hazards models adjusting for potential baseline confounders, P-wave terminal force in lead V1 was more strongly associated with incident stroke (hazard ratio per 1 SD increase, 1.21; 95% confidence interval, 1.02-1.44) than with incident AF (hazard ratio per 1 SD, 1.11; 95% confidence interval, 1.03-1.21). The association between P-wave terminal force in lead V1 and stroke was robust in numerous sensitivity analyses accounting for AF, including analyses that excluded those with any incident AF or modeled any incident AF as having been present from baseline. We found an association between baseline P-wave morphology and incident stroke even after accounting for AF. This association may reflect an atrial cardiopathy that leads to stroke in the absence of AF. © 2014 American Heart Association, Inc.

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.

Arrhythmia Termination Versus Elimination of Dormant Pulmonary Vein Conduction as a Procedural End Point of Catheter Ablation for Paroxysmal Atrial Fibrillation: A Prospective Randomized Trial.

PubMed

Theis, Cathrin; Konrad, Torsten; Mollnau, Hanke; Sonnenschein, Sebastian; Kämpfner, Denise; Potstawa, Maik; Ocete, Blanca Quesada; Bock, Karsten; Himmrich, Ewald; Münzel, Thomas; Rostock, Thomas

2015-10-01

Pulmonary vein isolation (PVI) is still associated with a substantial number of arrhythmia recurrences in paroxysmal atrial fibrillation (AF). This prospective, randomized study aimed to compare 2 different procedural strategies. A total of 152 patients undergoing de novo ablation for paroxysmal AF were randomized to 2 different treatment arms. The procedure in group A consisted of PVI exclusively. In this group, all isolated PVs were challenged with adenosine to reveal and ablate dormant conduction. In group B, PVI was performed with the patient either in spontaneous or in induced AF. If AF did not terminate with PVI, ablation was continued by targeting extra-PV AF sources with the desired procedural end point of termination to sinus rhythm. Primary study end point was freedom from arrhythmia during 1-year follow-up. In group A, adenosine provoked dormant conduction in 31 (41%) patients with a mean of 1.6±0.8 transiently recovered PVs per patient. Termination of AF during PVI was observed in 31 (65%) patients, whereas AF persisted afterward in 17 (35%) patients. AF termination occurred in 13 (76%) patients by AF source ablation. After 1-year follow-up, significantly more group B patients were free of arrhythmia recurrences (87 versus 68%; P=0.006). During redo ablation, the rate of PV reconduction did not differ between both groups (group A: 55% versus group B: 61%; P=0.25). Elimination of extra-PV AF sources after PVI is superior to sole PV isolation with the adjunct of abolishing potential dormant conduction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02238392. © 2015 The Authors.

Atrial ectopy predicts late recurrence of atrial fibrillation after pulmonary vein isolation.

PubMed

Gang, Uffe J O; Nalliah, Chrishan J; Lim, Toon Wei; Thiagalingam, Aravinda; Kovoor, Pramesh; Ross, David L; Thomas, Stuart P

2015-06-01

Late recurrence of atrial fibrillation (AF) after radiofrequency ablation remains significant. Asymptomatic recurrence poses a difficult clinical problem as it is associated with an equally increased risk of stroke and death compared with symptomatic AF events. Meta-analyses reveal that no single preablation patient characteristic efficiently predicts these AF recurrences. This study aimed to evaluate the prognostic value of premature atrial complex (PAC) occurrence with regard to the risk of late AF recurrence after radiofrequency ablation. The study cohort consisted of 124 patients with 7-day Holter recordings at 6 months post radiofrequency ablation for AF. No patients had AF recurrence before this time. Patients were followed-up every 6 months. Holter-detected PACs were defined as any supraventricular complexes occurring >30% earlier than expected. During a median follow-up of 4.2 years (first quartile to third quartile [Q1-Q3]=1.6-4.5), 32 patients (26%) had late recurrences of AF at a median of 462 days (Q1-Q3=319-1026) post radiofrequency ablation. The number of PACs per 24 hours was 248 (Q1-Q3=62-1026) in patients with and 77 (Q1-Q3=24-448) in patients without recurrence of AF (P=0.02). Multivariate analysis of the risk of late AF recurrence found ≥142 PACs per 24 hours to have a hazard ratio 2.84 (confidence interval, 1.26-6.43), P=0.01. This study showed that occurrence of ≥142 PACs per day at 6 months after PVI was independently associated with a significantly increased risk of late AF recurrence. These results could have important clinical implications for the design of post-PVI follow-up. URL: http://www.anzctr.org.au. Unique identifier: ACRTN12606000467538. © 2015 American Heart Association, Inc.

Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060

PubMed Central

Krijthe, Bouwe P.; Kunst, Anton; Benjamin, Emelia J.; Lip, Gregory Y.H.; Franco, Oscar H.; Hofman, Albert; Witteman, Jacqueline C.M.; Stricker, Bruno H.; Heeringa, Jan

2013-01-01

Aims Since atrial fibrillation (AF) is associated with increased risks of cardiovascular and cerebrovascular complications, estimations on the number of individuals with AF are relevant to healthcare planning. We aimed to project the number of individuals with AF in the Netherlands and in the European Union from 2000 to 2060. Methods and results Age- and sex-specific AF prevalence estimates were obtained from the prospective community-based Rotterdam Study. Population projections for the Netherlands and the European Union were obtained from the European Union's statistics office. In the age stratum of 55–59 years, the prevalence of AF was 1.3% in men (95% CI: 0.4–3.6%) and 1.7% in women (95% CI: 0.7–4.0%). The prevalence of AF increased to 24.2% in men (95% CI: 18.5–30.7%), and 16.1% in women (95% CI: 13.1–19.4%), for those >85 years of age. This age- and sex-specific prevalence remained stable during the years of follow-up. Furthermore, we estimate that in the European Union, 8.8 million adults over 55 years had AF in 2010 (95% CI: 6.5–12.3 million). We project that this number will double by 2060 to 17.9 million (95% CI: 13.6–23.7 million) if the age- and sex-specific prevalence remains stable. Conclusion We estimate that from 2010 to 2060, the number of adults 55 years and over with AF in the European Union will more than double. As AF is associated with significant morbidities and mortality, this increasing number of individuals with AF may have major public health implications. PMID:23900699

Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060.

PubMed

Krijthe, Bouwe P; Kunst, Anton; Benjamin, Emelia J; Lip, Gregory Y H; Franco, Oscar H; Hofman, Albert; Witteman, Jacqueline C M; Stricker, Bruno H; Heeringa, Jan

2013-09-01

Since atrial fibrillation (AF) is associated with increased risks of cardiovascular and cerebrovascular complications, estimations on the number of individuals with AF are relevant to healthcare planning. We aimed to project the number of individuals with AF in the Netherlands and in the European Union from 2000 to 2060. Age- and sex-specific AF prevalence estimates were obtained from the prospective community-based Rotterdam Study. Population projections for the Netherlands and the European Union were obtained from the European Union's statistics office. In the age stratum of 55-59 years, the prevalence of AF was 1.3% in men (95% CI: 0.4-3.6%) and 1.7% in women (95% CI: 0.7-4.0%). The prevalence of AF increased to 24.2% in men (95% CI: 18.5-30.7%), and 16.1% in women (95% CI: 13.1-19.4%), for those >85 years of age. This age- and sex-specific prevalence remained stable during the years of follow-up. Furthermore, we estimate that in the European Union, 8.8 million adults over 55 years had AF in 2010 (95% CI: 6.5-12.3 million). We project that this number will double by 2060 to 17.9 million (95% CI: 13.6-23.7 million) if the age- and sex-specific prevalence remains stable. We estimate that from 2010 to 2060, the number of adults 55 years and over with AF in the European Union will more than double. As AF is associated with significant morbidities and mortality, this increasing number of individuals with AF may have major public health implications.

Quantitative fundus autofluorescence in recessive Stargardt disease.

PubMed

Burke, Tomas R; Duncker, Tobias; Woods, Russell L; Greenberg, Jonathan P; Zernant, Jana; Tsang, Stephen H; Smith, R Theodore; Allikmets, Rando; Sparrow, Janet R; Delori, François C

2014-05-01

To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). A total of 42 STGD1 patients (ages: 7-52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials.

Quantitative Fundus Autofluorescence in Recessive Stargardt Disease

PubMed Central

Burke, Tomas R.; Duncker, Tobias; Woods, Russell L.; Greenberg, Jonathan P.; Zernant, Jana; Tsang, Stephen H.; Smith, R. Theodore; Allikmets, Rando; Sparrow, Janet R.; Delori, François C.

2014-01-01

Purpose. To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). Methods. A total of 42 STGD1 patients (ages: 7–52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. Results. Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. Conclusions. Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials. PMID:24677105

Birth weight and the risk of atrial fibrillation in whites and African Americans: the Atherosclerosis Risk In Communities (ARIC) study.

PubMed

Lawani, Sherifat O; Demerath, Ellen W; Lopez, Faye L; Soliman, Elsayed Z; Huxley, Rachel R; Rose, Kathryn M; Alonso, Alvaro

2014-05-26

Low birth weight (LBW) has been associated with an increased risk of cardiovascular disease (CVD). A previous study, however, found higher risk of atrial fibrillation (AF) in individuals with higher birth weight (BW). To further understand this apparent paradox, we examined the relationship between AF and BW in the Atherosclerosis Risk in Communities (ARIC) cohort. The analysis included 10,132 individuals free of AF at baseline (1996-1998), who provided BW information, were not born premature, and were not a twin. Self-reported BW was categorized as low (<2.5 kg), medium (2.5-4 kg), and high (>4.0 kg). AF incidence was ascertained from hospital discharge codes and death certificates. We used multivariable Cox proportional hazard models to determine the hazard ratios (HR) and 95% confidence intervals (CI) of AF across BW groups. During an average follow-up of 10.3 years, we identified 882 incident AF cases. LBW was associated with higher risk of AF. Compared to individuals in the medium BW category, the HR (95% CI) of AF was 1.33 (0.99, 1.78) for LBW and 1.00 (0.81, 1.24) for high BW after adjusting for sociodemographic variables (p for trend = 0.29). Additional adjustment for CVD risk factors did not attenuate the associations (HR 1.42, 95% CI 1.06, 1.90 for LBW and HR 0.86, 95% CI 0.69-1.07 for high BW, compared to medium BW, p for trend = 0.01). LBW was associated with a higher risk of AF. This association was independent of known predictors of AF and is consistent with that observed for other cardiovascular diseases.