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.

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.

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.

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.

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

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping

PubMed Central

Zaman, Junaid A. B.; Narayan, Sanjiv M.

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes. PMID:26306123

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping.

PubMed

Zaman, Junaid A B; Narayan, Sanjiv M

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

Lifestyle Therapy for the Management of Atrial Fibrillation.

PubMed

Abdul-Aziz, Ahmad A; Altawil, Mahmoud; Lyon, Amanda; MacEachern, Mark; Richardson, Caroline R; Rubenfire, Melvyn; Pelosi, Frank; Jackson, Elizabeth A

2018-05-01

Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of morbidity and mortality. There is evidence that lifestyle interventions may serve as complementary treatments to reduce AF burden. The objective of this review was to summarize the efficacy of lifestyle interventions for the management of AF. Studies which included patients with systolic heart failure (ejection fraction ≤40%), and those limited to an examination of vigorous physical activity were excluded from our search. Studies were identified through a search of the following databases: MEDLINE, EMBASE, CINAHIL, and PubMed, run from inception through August 2016. All studies were graded for quality using the Oxford Centre for Evidence-based Medicine recommendations. Meta-analyses of the studies were not performed due to the heterogeneity of the studies. From a total of 1,811 publications, 10 articles were identified and included. Selected publications included 1 study on yoga, 2 studies on acupuncture, 3 studies that examined weight loss programs, and 4 studies that evaluated the impact of moderate physical activity. Yoga was associated with less symptomatic AF episodes and improved quality of life. Acupuncture was associated with reduced AF occurrence in patients with persistent and paroxysmal AF. Weight loss was associated with a significant reduction AF burden and symptoms. Moderate exercise resulted in greater arrhythmia free survival and a mean reduction in AF burden. In conclusion, evidence exists to suggest that yoga, weight loss, and moderate exercise are associated with reductions in AF burden and symptoms. Evidence is greatest for weight loss and moderate exercise. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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.

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.

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

Chocolate consumption and risk of atrial fibrillation: Two cohort studies and a meta-analysis.

PubMed

Larsson, Susanna C; Drca, Nikola; Jensen-Urstad, Mats; Wolk, Alicja

2018-01-01

Chocolate consumption has been inconsistently associated with risk of atrial fibrillation (AF). We investigated the association between chocolate consumption and risk of AF in Swedish adults from two cohort studies and conducted a meta-analysis to summarize available evidence from cohort studies on this topic. Our study population comprised 40,009 men from the Cohort of Swedish Men and 32,486 women from the Swedish Mammography Cohort. Incident AF cases were ascertained through linkage with the Swedish National Patient Register. Published cohort studies of chocolate consumption in relation to risk of AF were identified by a PubMed search through September 14, 2017. During a mean follow-up of 14.6 years, AF was diagnosed in 9978 Swedish men and women. Compared with non-consumers, the multivariable hazard ratio of AF for those in the highest category of chocolate consumption (≥3-4 servings/week) was 0.96 (95% CI 0.88-1.04). In a random-effects meta-analysis of 5 cohort studies, including 180,454 participants and 16,356 AF cases, the hazard ratios of AF were 0.97 (95% CI 0.94-1.01) per 2 servings/week increase in chocolate consumption and 0.96 (95% CI 0.90-1.03) for the highest versus lowest category of chocolate consumption. Available data provide no evidence of an association of chocolate consumption with risk of AF. Copyright © 2017 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

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.

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

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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

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.

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.

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.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Atrial fibrillation in patients with gastroesophageal reflux disease: a comprehensive review.

PubMed

Roman, Crina; Bruley des Varannes, Stanislas; Muresan, Lucian; Picos, Alina; Dumitrascu, Dan L

2014-07-28

To analyze the potential relationship between gastroesophageal reflux disease (GERD) and the development of atrial fibrillation (AF). Using the key words "atrial fibrillation and gastroesophageal reflux", "atrial fibrillation and esophagitis, peptic", "atrial fibrillation and hernia, hiatal" the PubMed, EMBASE, Cochrane Library, OVIDSP, WILEY databases were screened for relevant publications on GERD and AF in adults between January 1972-December 2013. Studies written in languages other than English or French, studies not performed in humans, reviews, case reports, abstracts, conference presentations, letters to the editor, editorials, comments and opinions were not taken into consideration. Articles treating the subject of radiofrequency ablation of AF and the consecutive development of GERD were also excluded. Two thousand one hundred sixty-one titles were found of which 8 articles met the inclusion criteria. The presence of AF in patients with GERD was reported to be between 0.62%-14%, higher compared to those without GERD. Epidemiological data provided by these observational studies showed that patients with GERD, especially those with more severe GERD-related symptoms, had an increased risk of developing AF compared with those without GERD, but a causal relationship between GERD and AF could not be established based on these studies. The mechanisms of AF as a consequence of GERD remain largely unknown, with inflammation and vagal stimulation playing a possible role in the development of these disorders. Treatment with proton pomp inhibitors may improve symptoms related to AF and facilitate conversion to sinus rhythm. Although links between AF and GERD exist, large randomized clinical studies are required for a better understanding of the relationship between these two entities.

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.

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.

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.

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.

Low Serum Magnesium and the Development of Atrial Fibrillation in the Community: The Framingham Heart Study

PubMed Central

Khan, Abigail May; Lubitz, Steven A.; Sullivan, Lisa M.; Sun, Jenny X.; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; Ellinor, Patrick T.; Benjamin, Emelia J.; Wang, Thomas J.

2012-01-01

Background Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) following cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community. Methods and Results We studied 3,530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination, and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dl. The age- and sex-adjusted incidence rate of AF was 9.4 per 1,000 person-years (95% confidence interval, 6.7 to 11.9) in the lowest quartile of serum magnesium (≤1.77 mg/dl), compared with 6.3 per 1,000 person-years (95% confidence interval, 4.1 to 8.4) in the highest quartile (≥1.99 mg/dl). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were approximately 50% more likely to develop AF (adjusted hazard ratio, 1.52, 1.00 to 2.31; P=0.05), compared with those in the upper quartiles. Results were similar after excluding individuals on diuretics. Conclusion Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms. PMID:23172839

Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial.

PubMed

Diederichsen, Søren Zöga; Haugan, Ketil Jørgen; Køber, Lars; Højberg, Søren; Brandes, Axel; Kronborg, Christian; Graff, Claus; Holst, Anders Gaarsdal; Nielsen, Jonas Bille; Krieger, Derk; Svendsen, Jesper Hastrup

2017-05-01

Atrial fibrillation (AF) increases the rate of stroke 5-fold, and AF-related strokes have a poorer prognosis compared with non-AF-related strokes. Atrial fibrillation and stroke constitute an intensifying challenge, and health care organizations are calling for awareness on the topic. Previous studies have demonstrated that AF is often asymptomatic and consequently undiagnosed. The implantable loop recorder (ILR) allows for continuous, long-term electrocardiographic monitoring with daily transmission of arrhythmia information, potentially leading to improvement in AF detection and stroke prevention. The LOOP study is an investigator-initiated, randomized controlled trial with 6,000 participants randomized 3:1 to a control group or to receive an ILR with continuous electrocardiographic monitoring. Participants are identified from Danish registries and are eligible for inclusion if 70years or older and previously diagnosed as having at least one of the following conditions: hypertension, diabetes mellitus, heart failure, or previous stroke. Exclusion criteria include history of AF and current oral anticoagulation treatment. When an AF episode lasting ≥6minutes is detected, oral anticoagulation will be initiated according to guidelines. Expected follow-up is 4years. The primary end point is time to stroke or systemic embolism, whereas secondary end points include time to AF diagnosis and death. The LOOP study will evaluate health benefits and cost-effectiveness of ILR as a screening tool for AF to prevent stroke in patients at risk. Secondary objectives include identification of risk factors for the development of AF and characterization of arrhythmias in the population. The trial holds the potential to influence the future of stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Absorption and emission spectroscopic characterisation of 8-amino-riboflavin

NASA Astrophysics Data System (ADS)

Tyagi, A.; Zirak, P.; Penzkofer, A.; Mathes, T.; Hegemann, P.; Mack, M.; Ghisla, S.

2009-10-01

The flavin dye 8-amino-8-demethyl- D-riboflavin (AF) in the solvents water, DMSO, methanol, and chloroform/DMSO was studied by absorption and fluorescence spectroscopy. The first absorption band is red-shifted compared to riboflavin, and blue-shifted compared to roseoflavin (8-dimethylamino-8-demethyl-D-riboflavin). The fluorescence quantum yield of AF in the studied solvents varies between 20% and 50%. The fluorescence lifetimes were found to be in the 2-5 ns range. AF is well soluble in DMSO, weakly soluble in water and methanol, and practically insoluble in chloroform. The limited solubility causes AF aggregation, which was seen in differences between measured absorption spectra and fluorescence excitation spectra. Light scattering in the dye absorption region is discussed and approximate absorption cross-section spectra are determined from the combined measurement of transmission and fluorescence excitation spectra. The photo-stability of AF was studied by prolonged light exposure. The photo-degradation routes of AF are discussed.

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.

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.

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.

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

Clinical impact of rotor ablation in atrial fibrillation: a systematic review.

PubMed

Parameswaran, Ramanathan; Voskoboinik, Aleksandr; Gorelik, Alexandra; Lee, Geoffrey; Kistler, Peter M; Sanders, Prashanthan; Kalman, Jonathan M

2018-01-11

Rotor mapping and ablation have gained favour over the recent years as an emerging ablation strategy targeting drivers of atrial fibrillation (AF). Their efficacy, however, has been a topic of great debate with variable outcomes across centres. The aim of this study was to systematically review the recent medical literature to determine the medium-term outcomes of rotor ablation in patients with paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (PeAF). A systematic search of the contemporary scientific literature (PubMed and EMBASE) was performed in August 2017. Only studies assessing arrhythmia-free survival from rotor ablation of AF were included. We used the random-effects model to assess the primary outcome of pooled medium-term single-procedure AF-free survival for both PAF and PeAF. Success rates from multiple procedures and complication rates were also examined. We included 11 observational studies (4 PAF and 10 PeAF) with a total of 556 patients (166 PAF and 390 PeAF). Pooled single-procedure freedom from AF was 37.8% [95% confidence interval 5.6-86.3%] at a mean follow-up period of 13.8 ± 1.8 months for PAF and 59.2% (95% CI 41.4-74.9%) at a mean follow-up period of 12.9 ± 6 months for PeAF. There was a marked heterogeneity between studies (I2 = 93.8% for PAF and 88.3% for PeAF). The mean complication rate of rotor ablation among the reported studies was 3.4%. The wide variability in success rate between different centres performing rotor ablations suggests that the optimal ablation strategy, particularly targeting rotors, is unclear. Results from randomized studies are necessary before this technique can be considered as an established clinical tool. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

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

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.

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.

South Asian ethnicity is associated with a lower prevalence of atrial fibrillation despite greater prevalence of established risk factors: a population-based study in Bradford Metropolitan District.

PubMed

Gillott, Richard Geoffrey; Willan, Kathryn; Kain, Kirti; Sivananthan, Uduvil Mohanaraj; Tayebjee, Muzahir Hassan

2017-03-01

Previous studies indicate that South Asians (SAs) may have a reduced risk of developing atrial fibrillation (AF) despite having a higher prevalence of traditional cardiovascular risk factors. This observational study was designed to explore the relative differences between SAs and Whites in a well-defined, multi-ethnic population with careful consideration of traditional cardiovascular risk factors that are thought to contribute to the development of AF. Anonymized data from 417 575 adults were sourced from primary care records within Bradford Metropolitan District, UK. Atrial fibrillation diagnosis was indicated by the presence on the AF Quality Outcomes Framework register. Self-reported ethnicity was mapped to census ethnic codes. The age-standardized prevalence rates of AF were calculated for comparison between the White and SA populations; our study sample presented relative proportions of 2.39 and 0.4%. Multivariable logistic regression analysis was performed to estimate the odds of developing AF given SA ethnicity. Adjustment for age, sex, and established risk factors found a 71% reduction in odds of AF in SAs when compared with Whites [odds ratio (OR): 0.29, 95% confidence interval (CI): 0.26-0.32]. When stratified by ethnicity, analyses revealed significantly different odds of AF for patients with diabetes; diabetes was not associated with the development of AF in the SA population (0.81, 95% CI: 0.63-1.05). This study, in a multi-ethnic population, presents ethnicity as a predictor of AF in which prevalence is significantly lower in SAs when compared with Whites. This is despite SAs having a higher frequency of established risk factors for the development of AF, such as ischaemic heart disease, heart failure, hypertension, and type 2 diabetes. These findings are consistent with previous literature and add weight to the need for further investigation, although this is the first study to investigate the differential associations of individual risk factors with development of AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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.

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

PubMed

Zhao, Xinyu; Xia, Song; Chen, Youxin

2018-06-01

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

Quality of Life in Atrial Fibrillation: Measurement Tools and Impact of Interventions

PubMed Central

REYNOLDS, MATTHEW R.; ELLIS, ETHAN; ZIMETBAUM, PETER

2008-01-01

QoL in AF. Quality of life (QoL) is of central importance in atrial fibrillation as both a treatment goal and an endpoint in the evaluation of new therapies. QoL appears to be impaired in the majority of patients with AF. A number of interventions for AF have been shown to improve QoL, including pharmacologic and nonpharmacologic rate control, antiarrhythmic drugs, and nonpharmacologic rhythm control strategies. This paper will review the rationale, design, strengths, and limitations of the questionnaires most commonly used to assess QoL in AF studies, and present QoL outcomes from major studies of AF interventions. PMID:18266667

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.

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.

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.

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 burden of proof: The current state of atrial fibrillation prevention and treatment trials

PubMed Central

Zakeri, Rosita; Van Wagoner, David R.; Calkins, Hugh; Wong, Tom; Ross, Heather M.; Heist, E. Kevin; Meyer, Timothy E.; Kowey, Peter R.; Mentz, Robert J.; Cleland, John G.; Pitt, Bertram; Zannad, Faiez; Linde, Cecilia

2017-01-01

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015. PMID:28161513

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

PubMed

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

2007-11-15

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

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.

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.

From changes in local RAAS to structural remodeling of the left atrium: A beautiful cycle in atrial fibrillation.

PubMed

Yongjun, Q; Huanzhang, S; Wenxia, Z; Hong, T; Xijun, X

2015-05-01

In earlier studies, we reported structural remodeling was associated with atrial fibrillation (AF) and showed that the renin-angiotensin-aldosterone system (RAAS) was linked to AF. It is reasonable to hypothesize that there is a cycle, from RAAS to structural remodeling to AF. Our study group consisted of 80 patients scheduled for mitral valve replacement surgery. Tissue samples of the left atrial appendages were obtained. Masson's trichrome staining and immunohistochemical staining were performed to assess the extent of fibrosis. Radioimmunoassay was carried out to investigate the expression levels of local RAAS. RAAS-related genes were analyzed by RT-PCR. There was a significantly increased degree of fibrosis in AF patients compared with sinus rhythm (SR) patients (p = 0.023). There were significant differences in the expression levels of local angiotensin (Ang) II between the SR and the AF groups (p = 0.002). The expression levels of local Ang II correlated with the duration of AF (r = 0.727851, p = 0.001) and with collagen type I (r = 0.672189, p = 0.032). In the AF group, the mRNA expressions of the AT1R and ACE genes were markedly up-regulated in comparison with the SR group (p = 0.021 and p = 0.037). On the basis of this study, and in combination with results of our previous studies, we demonstrate for the first time that there is a cycle involving RAAS, structural remodeling, and AF. RAAS, structural remodeling, and AF are the principal aspects in this cycle.

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.

Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

PubMed Central

Kumari, Mandavi; Sachar, Sumedha; Saxena, Rajiv K.

2012-01-01

Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells. PMID:22384094

Atrial fibrillation in patients with gastroesophageal reflux disease: A comprehensive review

PubMed Central

Roman, Crina; Bruley des Varannes, Stanislas; Muresan, Lucian; Picos, Alina; Dumitrascu, Dan L

2014-01-01

AIM: To analyze the potential relationship between gastroesophageal reflux disease (GERD) and the development of atrial fibrillation (AF). METHODS: Using the key words “atrial fibrillation and gastroesophageal reflux”, “atrial fibrillation and esophagitis, peptic”, “atrial fibrillation and hernia, hiatal” the PubMed, EMBASE, Cochrane Library, OVIDSP, WILEY databases were screened for relevant publications on GERD and AF in adults between January 1972-December 2013. Studies written in languages other than English or French, studies not performed in humans, reviews, case reports, abstracts, conference presentations, letters to the editor, editorials, comments and opinions were not taken into consideration. Articles treating the subject of radiofrequency ablation of AF and the consecutive development of GERD were also excluded. RESULTS: Two thousand one hundred sixty-one titles were found of which 8 articles met the inclusion criteria. The presence of AF in patients with GERD was reported to be between 0.62%-14%, higher compared to those without GERD. Epidemiological data provided by these observational studies showed that patients with GERD, especially those with more severe GERD-related symptoms, had an increased risk of developing AF compared with those without GERD, but a causal relationship between GERD and AF could not be established based on these studies. The mechanisms of AF as a consequence of GERD remain largely unknown, with inflammation and vagal stimulation playing a possible role in the development of these disorders. Treatment with proton pomp inhibitors may improve symptoms related to AF and facilitate conversion to sinus rhythm. CONCLUSION: Although links between AF and GERD exist, large randomized clinical studies are required for a better understanding of the relationship between these two entities. PMID:25071357

European Ancestry as a Risk Factor for Atrial Fibrillation in African Americans

PubMed Central

Marcus, Gregory M.; Alonso, Alvaro; Peralta, Carmen A.; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A.; Fox, Ervin R.; Levitzky, Yamini S.; Mehra, Reena; Kerr, Kathleen F.; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T.; Paltoo, Dina N.; Soliman, Elsayed Z.; Benjamin, Emelia J.; Heckbert, Susan R.

2010-01-01

Background Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown if the higher riskis due to genetic or environmental factors. As African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. Methods and Results We studied whites (n=4,543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10,902) and Africa Americans (n=3,517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3,517). Percent European ancestry in African Americans was estimated using 1,747 ancestry informative markers (AIMs) from the Illumina custom ITMAT-Broad-CARe (IBC) array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3,517 ARIC participants developed incident AF. A meta-analysis from the two studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (HR 1.13, 95% CI 1.03–1.23, p=0.007). After adjusting for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% CI 1.07–1.29, p=0.001). A second analysis using 3,192 AIMs from a genome wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. Conclusion European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative. PMID:21098467

European ancestry as a risk factor for atrial fibrillation in African Americans.

PubMed

Marcus, Gregory M; Alonso, Alvaro; Peralta, Carmen A; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A; Fox, Ervin R; Levitzky, Yamini S; Mehra, Reena; Kerr, Kathleen F; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T; Paltoo, Dina N; Soliman, Elsayed Z; Benjamin, Emelia J; Heckbert, Susan R

2010-11-16

Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P=0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29; P=0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative.

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.

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

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.

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

Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis.

PubMed

Baykaner, Tina; Rogers, Albert J; Meckler, Gabriela L; Zaman, Junaid; Navara, Rachita; Rodrigo, Miguel; Alhusseini, Mahmood; Kowalewski, Christopher A B; Viswanathan, Mohan N; Narayan, Sanjiv M; Clopton, Paul; Wang, Paul J; Heidenreich, Paul A

2018-05-01

The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure. Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I 2 statistic. Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%-81.8%; P <0.01) and from all arrhythmias of 57.8% (CI, 47.5%-67.7%; P <0.01). AF driver ablation when added to PVI or as stand-alone procedure compared with controls produced an odds ratio of 3.1 (CI, 1.3-7.7; P =0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2-2.7; P <0.01) for freedom from all arrhythmias in 4 controlled studies. AF termination rate was 40.5% (CI, 30.6%-50.9%) and predicted favorable outcome from ablation( P <0.05). In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI. © 2018 American Heart Association, Inc.

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

PubMed

Anaszewicz, Marzena; Budzyński, Jacek

2017-05-01

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

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Feasibility of Using Mobile ECG Recording Technology to Detect Atrial Fibrillation in Low-Resource Settings.

PubMed

Evans, Grahame F; Shirk, Arianna; Muturi, Peter; Soliman, Elsayed Z

2017-12-01

Screening for atrial fibrillation (AF), a major risk factor for stroke that is on the rise in Africa, is becoming increasingly critical. This study sought to examine the feasibility of using mobile electrocardiogram (ECG) recording technology to detect AF. In this prospective observational study, we used a mobile ECG recorder to screen 50 African adults (66% women; mean age 54.3 ± 20.5 years) attending Kijabe Hospital (Kijabe, Kenya). Five hospital health providers involved in this study's data collection process also completed a self-administered survey to obtain information on their access to the Internet and mobile devices, both factors necessary to implement ECG mobile technology. Outcome measures included feasibility (completion of the study and recruitment of the patients on the planned study time frame) and the yield of the screening by the mobile ECG technology (ability to detect previously undiagnosed AF). Patients were recruited in a 2-week period as planned; only 1 of the 51 patients approached refused to participate (98% acceptance rate). All of the 50 patients who agreed to participate completed the test and produced readable ECGs (100% study completion rate). ECG tracings of 4 of the 50 patients who completed the study showed AF (8% AF yield), and none had been previously diagnosed with AF. When asked about continuous access to Internet and personal mobile devices, almost all of the health care providers surveyed answered affirmatively. Using mobile ECG technology in screening for AF in low-resource settings is feasible, and can detect a significant proportion of AF cases that will otherwise go undiagnosed. Further study is needed to examine the cost-effectiveness of this approach for detection of AF and its effect on reducing the risk of stroke in developing countries. Copyright © 2016 World Heart Federation (Geneva). Published by Elsevier B.V. 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.

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.

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.

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.

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

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

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.

Multistage electrotherapy delivered through chronically-implanted leads terminates atrial fibrillation with lower energy than a single biphasic shock.

PubMed

Janardhan, Ajit H; Gutbrod, Sarah R; Li, Wenwen; Lang, Di; Schuessler, Richard B; Efimov, Igor R

The goal of this study was to develop a low-energy, implantable device-based multistage electrotherapy (MSE) to terminate atrial fibrillation (AF). Previous attempts to perform cardioversion of AF by using an implantable device were limited by the pain caused by use of a high-energy single biphasic shock (BPS). Transvenous leads were implanted into the right atrium (RA), coronary sinus, and left pulmonary artery of 14 dogs. Self-sustaining AF was induced by 6 ± 2 weeks of high-rate RA pacing. Atrial defibrillation thresholds of standard versus experimental electrotherapies were measured in vivo and studied by using optical imaging in vitro. The mean AF cycle length (CL) in vivo was 112 ± 21 ms (534 beats/min). The impedances of the RA-left pulmonary artery and RA-coronary sinus shock vectors were similar (121 ± 11 Ω vs. 126 ± 9 Ω; p = 0.27). BPS required 1.48 ± 0.91 J (165 ± 34 V) to terminate AF. In contrast, MSE terminated AF with significantly less energy (0.16 ± 0.16 J; p < 0.001) and significantly lower peak voltage (31.1 ± 19.3 V; p < 0.001). In vitro optical imaging studies found that AF was maintained by localized foci originating from pulmonary vein-left atrium interfaces. MSE Stage 1 shocks temporarily disrupted localized foci; MSE Stage 2 entrainment shocks continued to silence the localized foci driving AF; and MSE Stage 3 pacing stimuli enabled consistent RA-left atrium activation until sinus rhythm was restored. Low-energy MSE significantly reduced the atrial defibrillation thresholds compared with BPS in a canine model of AF. MSE may enable painless, device-based AF therapy. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Multistage Electrotherapy Delivered Through Chronically-Implanted Leads Terminates Atrial Fibrillation With Lower Energy Than a Single Biphasic Shock

PubMed Central

Janardhan, Ajit H.; Gutbrod, Sarah R.; Li, Wenwen; Lang, Di; Schuessler, Richard B.; Efimov, Igor R.

2014-01-01

Objectives The goal of this study was to develop a low-energy, implantable device–based multistage electrotherapy (MSE) to terminate atrial fibrillation (AF). Background Previous attempts to perform cardioversion of AF by using an implantable device were limited by the pain caused by use of a high-energy single biphasic shock (BPS). Methods Transvenous leads were implanted into the right atrium (RA), coronary sinus, and left pulmonary artery of 14 dogs. Self-sustaining AF was induced by 6 ± 2 weeks of high-rate RA pacing. Atrial defibrillation thresholds of standard versus experimental electrotherapies were measured in vivo and studied by using optical imaging in vitro. Results The mean AF cycle length (CL) in vivo was 112 ± 21 ms (534 beats/min). The impedances of the RA–left pulmonary artery and RA–coronary sinus shock vectors were similar (121 ± 11 Ω vs. 126 ± 9 Ω; p = 0.27). BPS required 1.48 ± 0.91 J (165 ± 34 V) to terminate AF. In contrast, MSE terminated AF with significantly less energy (0.16 ± 0.16 J; p < 0.001) and significantly lower peak voltage (31.1 ± 19.3 V; p < 0.001). In vitro optical imaging studies found that AF was maintained by localized foci originating from pulmonary vein–left atrium interfaces. MSE Stage 1 shocks temporarily disrupted localized foci; MSE Stage 2 entrainment shocks continued to silence the localized foci driving AF; and MSE Stage 3 pacing stimuli enabled consistent RA–left atrium activation until sinus rhythm was restored. Conclusions Low-energy MSE significantly reduced the atrial defibrillation thresholds compared with BPS in a canine model of AF. MSE may enable painless, device-based AF therapy. PMID:24076284

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

PubMed

Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D

2016-09-01

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. © 2016 American Heart Association, Inc.

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.

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.

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.

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

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.

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.

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.

Rivaroxaban in patients with atrial fibrillation: from ROCKET AF to everyday practice.

PubMed

Barón-Esquivias, Gonzalo; Marín, Francisco; Sanmartín Fernandez, Marcelo

2017-05-01

Registries and non-interventional studies offer relevant and complementary information to clinical trials, since they have a high external validity. Areas covered: The information regarding the efficacy and safety of rivaroxaban compared with warfarin, or rivaroxaban alone in clinical practice was reviewed in this manuscript. For this purpose, a search on MEDLINE and EMBASE databases was performed. The MEDLINE and EMBASE search included both medical subject headings (MeSH) and keywords including: atrial fibrillation (AF) OR warfarin OR clinical practice OR ROCKET AF AND rivaroxaban. Case reports were not considered. Expert commentary: In ROCKET AF, rivaroxaban was at least as effective as warfarin for the prevention of stroke in patients with nonvalvular AF at high risk of stroke, but, importantly, with a lesser risk of intracranial, critical and fatal bleedings. A number of observational comparative and non-comparative studies, with more than 60,000 patients included treated with rivaroxaban, have analyzed the efficacy and safety of rivaroxaban in real-life patients with AF in different clinical settings. These studies have shown that in clinical practice, rates of stroke and major bleeding were consistently lower than those reported in ROCKET AF, likely due to the lower thromboembolic and bleeding risk observed in these patients.

Investigation of selection bias in the association of race with prevalent atrial fibrillation in a national cohort study: REasons for Geographic And Racial Differences in Stroke (REGARDS).

PubMed

Thacker, Evan L; Soliman, Elsayed Z; Pulley, LeaVonne; Safford, Monika M; Howard, George; Howard, Virginia J

2016-08-01

Atrial fibrillation (AF) is diagnosed more commonly in whites than blacks in the United States. In epidemiologic studies, selection bias could induce a noncausal positive association of white race with prevalent AF if voluntary enrollment was influenced by both race and AF status. We investigated whether nonrandom enrollment biased the association of race with prevalent self-reported AF in the US-based REasons for Geographic And Racial Differences in Stroke Study (REGARDS). REGARDS had a two-stage enrollment process, allowing us to compare 30,183 fully enrolled REGARDS participants with 12,828 people who completed the first-stage telephone survey but did not complete the second-stage in-home visit to finalize their REGARDS enrollment (telephone-only participants). REGARDS enrollment was higher among whites (77.1%) than among blacks (62.3%) but did not differ by self-reported AF status. The prevalence of AF was 8.45% in whites and 5.86% in blacks adjusted for age, sex, income, education, and perceived general health. The adjusted white/black prevalence ratio of self-reported AF was 1.43 (95% CI, 1.32-1.56) among REGARDS participants and 1.38 (1.22-1.55) among telephone-only participants. These findings suggest that selection bias is not a viable explanation for the higher prevalence of self-reported AF among whites in population studies such as REGARDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of pulse pressure with new-onset atrial fibrillation in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study.

PubMed

Larstorp, Anne Cecilie K; Ariansen, Inger; Gjesdal, Knut; Olsen, Michael H; Ibsen, Hans; Devereux, Richard B; Okin, Peter M; Dahlöf, Björn; Kjeldsen, Sverre E; Wachtell, Kristian

2012-08-01

Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota coding of electrocardiograms confirmed new-onset AF in 353 patients (4.0%) during mean 4.9 years of follow-up. In multivariate Cox regression analyses, baseline and in-treatment PP and baseline and in-treatment systolic blood pressure predicted new-onset AF, independent of baseline age, height, weight, and Framingham Risk Score; sex, race, and treatment allocation; and in-treatment heart rate and Cornell product. PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the -2 Log likelihood statistic, in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new-onset AF, independent of other risk factors.

Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat with Incident Atrial Fibrillation (From the Framingham Heart Study)

PubMed Central

Lee, Jane J.; Yin, Xiaoyan; Hoffmann, Udo; Fox, Caroline S.; Benjamin, Emelia J.

2016-01-01

Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third Generation Cohorts who participated in the multi-detector computed tomography sub-study examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index (BMI) was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and sex-adjusted incident AF rate per 1000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and sex-adjusted model, greater pericardial fat [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.03-1.34] and intrathoracic fat (HR 1.24, 95% CI 1.06-1.45) were associated with increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99-1.30) for pericardial fat, 1.19 (1.01-1.40) for intrathoracic fat, and 1.09 (0.93-1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of BMI, none of the associations remained significant (all p>0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. PMID:27666172

Prevalence, incidence, risk factors and treatment of atrial fibrillation in Australia: The Australian Diabetes, Obesity and Lifestyle (AusDiab) longitudinal, population cohort study.

PubMed

Diouf, Ibrahima; Magliano, Dianna J; Carrington, Melinda J; Stewart, Simon; Shaw, Jonathan E

2016-02-15

We sought to describe the prevalence, incidence, risk factors and treatment (according to stroke risk) of atrial fibrillation (AF) in the national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study cohort. ECG data were available from 8273/11,247 participants of AusDiab study in 1999/2000 and from 5422 participants in 2004/2005. Minnesota coding was used to identify prevalent and incident cases of AF. 90 prevalent cases of AF (14.1 per 1000) comprising 56 men (mean age 70.5 ± 1.9 years) and 34 women (aged 78.3 ± 1.2 years) were identified in 1999-2000. AF prevalence was associated with sedentary behaviour versus physically active (PR 2.0, 95% CI 1.2-3.6). 53 incident cases of AF (2.0, 95%, CI 1.5-2.6 per 1000 person-year) were subsequently identified in 2004-2005. Increased risk of incident AF was associated with male sex, obesity, history of angina, myocardial infarction and stroke. Both increased weight gain and increased weight loss appeared to be associated with increased risks of developing AF in women, while no obvious association was observed in men. Despite their high risk for stroke, anti-thrombotic therapy was observed in only 39.3% of participants with CHA2DS2-VASC scores ≥ 2. This study contributes to a better understanding of the AF burden. With the ageing population, coordinated efforts will be needed to anticipate the future health care costs related to AF and its impacts on the health care system. This will include appropriate application of anti-thrombotic therapy according to risk of thrombo-embolic events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of authority figures for pedestrian evacuation at metro stations

NASA Astrophysics Data System (ADS)

Song, Xiao; Zhang, Zenghui; Peng, Gongzhuang; Shi, Guoqiang

2017-01-01

Most pedestrian evacuation literatures are about routing algorithm, human intelligence and behavior etc. Few works studied how to fully explore the function of authority/security figures, who know more of the environment by simply being there every day. To evaluate the effect of authority figure (AF) in complex buildings, this paper fully investigates the AF related factors that may influence the evacuation effect of crowd, such as the number and locations of AFs, their spread of direction, calming effect and distribution strategies etc. Social force based modeling and simulation results show that these factors of AFs play important roles in evacuation efficiency, which means fewer AFs with right guiding strategy can have good evacuation performance. For our case study, Zhichun Avenue station, the conclusion is that deployment of four AFs is a good choice to achieve relatively high evacuation performance yet save cost.

The burden of proof: The current state of atrial fibrillation prevention and treatment trials.

PubMed

Zakeri, Rosita; Van Wagoner, David R; Calkins, Hugh; Wong, Tom; Ross, Heather M; Heist, E Kevin; Meyer, Timothy E; Kowey, Peter R; Mentz, Robert J; Cleland, John G; Pitt, Bertram; Zannad, Faiez; Linde, Cecilia

2017-05-01

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3-5, 2015. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

Jang, Sung Ho

2013-01-01

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

Paroxysmal atrial fibrillation recognition based on multi-scale Rényi entropy of ECG.

PubMed

Xin, Yi; Zhao, Yizhang; Mu, Yuanhui; Li, Qin; Shi, Caicheng

2017-07-20

Atrial fibrillation (AF) is a common type of arrhythmia disease, which has a high morbidity and can lead to some serious complications. The ability to detect and in turn prevent AF is extremely significant to the patient and clinician. Using ECG to detect AF and develop a robust and effective algorithm is the primary objective of this study. Some studies show that after AF occurs, the regulatory mechanism of vagus nerve and sympathetic nerve will change. Each R-R interval will be absolutely unequal. After studying the physiological mechanism of AF, we will calculate the Rényi entropy of the wavelet coefficients of heart rate variability (HRV) in order to measure the complexity of PAF signals, as well as extract the multi-scale features of paroxysmal atrial fibrillation (PAF). The data used in this study is obtained from MIT-BIH PAF Prediction Challenge Database and the correct rate in classifying PAF patients from normal persons is 92.48%. The results of this experiment proved that AF could be detected by using this method and, in turn, provide opinions for clinical diagnosis.

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.

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

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

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.

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.

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.

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 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

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.

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.

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.

Autofluorescence-based diagnostic UV imaging of tissues and cells

NASA Astrophysics Data System (ADS)

Renkoski, Timothy E.

Cancer is the second leading cause of death in the United States, and its early diagnosis is critical to improving treatment options and patient outcomes. In autofluorescence (AF) imaging, light of controlled wavelengths is projected onto tissue, absorbed by specific molecules, and re-emitted at longer wavelengths. Images of re-emitted light are used together with spectral information to infer tissue functional information and diagnosis. This dissertation describes AF imaging studies of three different organs using data collected from fresh human surgical specimens. In the ovary study, illumination was at 365 nm, and images were captured at 8 emission wavelengths. Measurements from a multispectral imaging system and fiber optic probe were used to map tissue diagnosis at every image pixel. For the colon and pancreas studies, instrumentation was developed extending AF imaging capability to sub-300 nm excitation. Images excited in the deep UV revealed tryptophan and protein content which are believed to change with disease state. Several excitation wavelength bands from 280 nm to 440 nm were investigated. Microscopic AF images collected in the pancreas study included both cultured and primary cells. Several findings are reported. A method of transforming fiber optic probe spectra for direct comparison with imager spectra was devised. Normalization of AF data by green reflectance data was found useful in correcting hemoglobin absorption. Ratio images, both AF and reflectance, were formulated to highlight growths in the colon. Novel tryptophan AF images were found less useful for colon diagnostics than the new ratio techniques. Microscopic tryptophan AF images produce useful visualization of cellular protein content, but their diagnostic value requires further study.

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

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.

[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.

Advanced glycation end products, measured in skin, vs. HbA1c in children with type 1 diabetes mellitus.

PubMed

Banser, Alena; Naafs, Jolanda C; Hoorweg-Nijman, Jantine Jg; van de Garde, Ewoudt Mw; van der Vorst, Marja Mj

2016-09-01

Advanced glycation end products (AGEs) are considered major contributors to microvascular and macrovascular complications in adult patients with diabetes mellitus. AGEs can be measured non-invasively with skin autofluorescence (sAF). The primary aim was to determine sAF values in children with type 1 diabetes mellitus and to study correlations between sAF values and HbA1c and mean HbA1c over the year prior to measurement In children with type 1 diabetes mellitus, sAF values were measured using the AGE Reader®. Laboratory and anthropometric values were extracted from medical charts. Correlations were studied using Pearson's correlation coefficient. Multivariable linear regression analysis was conducted to evaluate the effect of multiple study parameters on sAF values. The mean sAF value was 1.33 ± 0.36 arbitrary units (AU) in children with type 1 diabetes mellitus (n = 144). sAF values correlated positively with HbA1c measured at the same time (r = 0.485; p < 0.001), mean HbA1c over the year prior to measurement (r = 0.578; p < 0.001), age (r = 0.337; p < 0.001), duration of type 1 diabetes mellitus (r = 0.277; p = 0.001), serum triglycerides (r = 0.399; p < 0.001), and total cholesterol (r = 0.352; p = 0.001). sAF values were significantly higher in patients with non-white skin (1.56 vs. 1.27 AU, respectively, p = 0.001). In children with type 1 diabetes, sAF values correlate strongly with single HbA1c and mean HbA1c, making the non-invasive sAF measurement an interesting alternative to provide information about cumulative hyperglycemic states. To determine the value of sAF measurement in predicting long-term microvascular and macrovascular complications, further prospective follow-up studies are needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

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.

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.

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.

Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source.

PubMed

Sanna, Tommaso; Ziegler, Paul D; Crea, Filippo

2018-03-01

Cryptogenic stroke (CS) and embolic stroke of unknown source (ESUS) represent a major challenge to healthcare systems worldwide. Atrial fibrillation (AF) is commonly found after CS or ESUS. Independent of the mechanism of the index CS or ESUS, detection of AF in these patients offers the opportunity to reduce the risk of stroke recurrence by prescribing an anticoagulant instead of aspirin. The detection of AF may be pursued with different monitoring strategies. Comparison of monitoring strategies should take into account that AF detection rates reported in published studies, and then pooled in meta-analyses, are not only a function of the monitoring strategy itself, but also depend on patient-related, device-related, and study design-related factors. Once AF is found, the decision to anticoagulate a patient should be made on the basis of AF burden and the baseline risk of the patient. Empirical anticoagulation in patients with ESUS and no evidence of AF is an intriguing but still-unproven strategy and therefore should not be adopted outside of randomized clinical trials. © 2018 Wiley Periodicals, Inc.

Atrial fibrillation driver mechanisms: Insight from the isolated human heart.

PubMed

Csepe, Thomas A; Hansen, Brian J; Fedorov, Vadim V

2017-01-01

Although there have been great technological advances in the treatment of atrial fibrillation (AF), current therapies remain limited due to a narrow understanding of AF mechanisms in the human heart. This review will highlight our recent studies on explanted human hearts where we developed and employed a novel functional-structural mapping approach by integrating high-resolution simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium-enhanced MRI to define the spatiotemporal characteristics of AF drivers and their structural substrates. The results allow us to postulate that the primary mechanism of AF maintenance in human hearts is a limited number of localized intramural microanatomic reentrant AF drivers anchored to heart-specific 3D fibrotically insulated myobundle tracks, which may remain hidden to clinical single-surface electrode mapping. We suggest that ex vivo human heart studies, by using an integrated 3D functional and structural mapping approach, will help to reveal defining features of AF drivers as well as validate and improve clinical approaches to detect and target these AF drivers in patients with cardiac diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

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.

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.

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.

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.

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.

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.

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

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

PubMed

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

2017-09-01

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

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

Association of atrial fibrillation and cancer: Analysis from two large population-based case-control studies.

PubMed

Saliba, Walid; Rennert, Hedy S; Gronich, Naomi; Gruber, Stephen B; Rennert, Gad

2018-01-01

An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this association remain unclear. Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF. AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases. Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.

Analysis of the Association Between Electrocardiographic P-wave Characteristics and Atrial Fibrillation in the REGICOR Study.

PubMed

Massó-van Roessel, Albert; Escobar-Robledo, Luis Alberto; Dégano, Irene R; Grau, María; Sala, Joan; Ramos, Rafel; Marrugat, Jaume; Bayés de Luna, Antoni; Elosua, Roberto

2017-10-01

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. P-wave duration and interatrial blocks (IAB) have been reported to be associated with AF. Our aim was to determine the individual and combined association of P-wave duration and advanced IAB morphology with AF. We designed an age-, sex-, and survey-matched case-control study nested in a population-based cohort (REGICOR: REgistre GIroní del COR). Two different surveys recruited a total of 9380 participants from 1999 to 2005; all participants were invited to a second examination between 2009 and 2013. For the present study, we selected participants aged 25 to 79 years with follow-up through the end of the study. All electrocardiograms were analyzed by 2 observers to determine P-wave duration and morphology (normal, partial, or advanced IAB). The median follow-up was 7.12 years. Eighty participants presented with AF, had a legible baseline electrocardiogram, and were included in the study, along with 160 controls. P-wave duration and the presence of partial or advanced IAB were associated with AF. When P-wave duration and morphology were considered together, only P-wave duration (≥ 110 milliseconds) showed an independent and strong association with AF. The odds ratio for AF of P-wave duration between 110-119, 120-129 and ≥ 130 milliseconds vs < 110 milliseconds were 5.33; 95%CI, 1.74-16.33, 5.08; 95%CI, 1.73-14.90 and 5.44; 95%CI, 1.95-15.15, respectively. A P-wave longer than 110 milliseconds increases the risk of AF. Advanced IAB morphology did not seem to provide an additional AF risk beyond that of P-wave duration. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Alpha-fetoprotein and its value for predicting pregnancy outcomes – a re-evaluation

PubMed Central

Darouich, Ayham Alhaj; Liehr, Thomas; Weise, Anja; Schlembach, Dietmar; Schleußner, Ekkehart; Kiehntopf, Michael; Schreyer, Isolde

2015-01-01

Introduction Alpha-fetoprotein (AFP) concentrations can be determined framing others from invasively acquired amnion fluid (AF-AFP). While the biological role of AFP remains unclear it is well known that AFP-levels can be altered in connection with specific clinical and/or genetic alterations of the fetus. Materials and Method here a retrospective study based on 3,119 singleton and 56 twin pregnancies is presented. The standard levels of amnion fluid derived alpha-fetoprotein level (AF-AFP) between 12th and 36th weeks of gestation were determined. Additionally, acetylcholinesterase (AChE) test results for 63 cases, ultrasonography results for 32 cases and abnormal karyotypic findings for 100 cases were available for selected cases. Results and Discussion according to the present data the AF-AFP test is reliable and provides expected test results in terms of population studies. However, individual AF-AFP test results can be subject to high individual variations. In this study AF-AFP multiple of medians (MoM) over 1.7 were indicative for neuronal tube defects and/or omphalocele in only 6.3% of the cases, while such AF-AFP values were hints on severe sonographic signs in 62% of the cases. Also, altered AF-AFP concentrations were present in 82% of cytogenetically abnormal cases. Overall, even though predicative value of the AF-AFP-test is matter of discussion it continues to be widely applied in invasive prenatal diagnostics. This study indicates that it only can be applied reliably in combination with other tests like banding cytogenetics, ultrasonography and all embedded in well-established genetic counseling. PMID:27358693

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.

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.

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.

Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study.

PubMed

Doyon, Caroline Y; Brochu, Martin; Messier, Virginie; Lavoie, Marie-Ève; Faraj, May; Doucet, Eric; Rabasa-Lhoret, Rémi; Dionne, Isabelle J

2011-01-01

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P < .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P < .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P < .01) or delta VF (r = 0.51; P < .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF.

Association between Abdominal Fat (DXA) and Its Subcomponents (CT Scan) before and after Weight Loss in Obese Postmenopausal Women: A MONET Study

PubMed Central

Doyon, Caroline Y.; Brochu, Martin; Messier, Virginie; Lavoie, Marie-Ève; Faraj, May; Doucet, Éric; Rabasa-Lhoret, Rémi; Dionne, Isabelle J.

2011-01-01

Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P < .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P < .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P < .01) or delta VF (r = 0.51; P < .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF. PMID:21603261

Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

PubMed

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

2012-01-01

The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

Can we spice up our Christmas dinner? : Busting the myth of the 'Chinese restaurant syndrome'.

PubMed

van den Berg, N W E; Neefs, J; Berger, W R; Baalman, S W E; Meulendijks, E; Kawasaki, M; Kemper, E M; Piersma, F R; Veldkamp, M W; Wesselink, R; Krul, S P J; de Groot, J R

2017-12-01

Monosodium glutamate (MSG), also referred to as Vetsin or E621, is a flavour enhancer frequently used in Asian cuisine and abundantly present in the famous Chinese dish Peking duck. MSG is notorious for triggering the onset of the so-called 'Chinese restaurant syndrome' (CRS), a complex of unpleasant symptoms, which might include flushing, sweating and the onset of atrial fibrillation (AF). This study aims to determine the effects of MSG on the occurrence of AF. We conducted a placebo self-controlled single-arm study in the Academic Medical Centre in Amsterdam. We included paroxysmal AF patients who reported a consistent onset of AF upon MSG intake. During three admissions, participants were subsequently administered: placebo, 1.5 g and 3 g MSG. If AF was recorded after the dose of 1.5 g MSG, patients were given another placebo instead of 3 g MSG. The primary outcome was the onset of AF registered by 24-hour Holter monitoring. The secondary outcomes were any other arrhythmia and the onset of CRS defined as two or more symptoms of CRS after MSG intake. Six men participated in the study. Both 1.5 g and 3 g MSG were unrelated to CRS, arrhythmias or AF occurrence. Peking duck can be put on the Christmas menu without risking guests to be admitted to the emergency department with new episodes of AF.

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

PubMed

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

2014-07-01

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

XANTUS: rationale and design of a noninterventional study of rivaroxaban for the prevention of stroke in patients with atrial fibrillation

PubMed Central

Camm, A John; Amarenco, Pierre; Haas, Sylvia; Hess, Susanne; Kirchhof, Paulus; van Eickels, Martin; Turpie, Alexander GG

2014-01-01

Atrial fibrillation (AF) is associated with a fivefold increase in the risk of stroke. The Phase III ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial showed that rivaroxaban, an oral, direct Factor Xa inhibitor, was noninferior to warfarin for the reduction of stroke or systemic embolism in patients with AF. Compared with warfarin, rivaroxaban significantly reduced rates of intracranial and fatal hemorrhages, although not rates of bleeding overall. XANTUS (Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation) is a prospective, international, observational, postauthorization, noninterventional study designed to collect safety and efficacy data on the use of rivaroxaban for stroke prevention in AF in routine clinical practice. The key goal is to determine whether the safety profile of rivaroxaban established in ROCKET AF is also observed in routine clinical practice. XANTUS is designed as a single-arm cohort study to minimize selection bias, and will enroll approximately 6,000 patients (mostly from Europe) with nonvalvular AF prescribed rivaroxaban, irrespective of their level of stroke risk. Overall duration of follow-up will be 1 year; the first patient was enrolled in June 2012. Similar studies (XANTUS-EL [Xarelto® for Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation, Eastern Europe, Middle East, Africa and Latin America] and XANAP [Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific]) are ongoing in Latin America and Asia-Pacific. Data from these studies will supplement those from ROCKET AF and provide practical information concerning the use of rivaroxaban for stroke prevention in AF. PMID:25083135

Advanced glycation end-products (AGEs) accumulation in skin: relations with chronic kidney disease-mineral and bone disorder.

PubMed

França, Renata de Almeida; Esteves, André de Barros Albuquerque; Borges, Cynthia de Moura; Quadros, Kélcia Rosana da Silva; Falcão, Luiz Carlos Nogueira; Caramori, Jacqueline Costa Teixeira; Oliveira, Rodrigo Bueno de

2017-01-01

Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients. Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

Cardiac Magnetic Resonance-Measured Left Atrial Volume and Function and Incident Atrial Fibrillation: Results From MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Habibi, Mohammadali; Samiei, Sanaz; Ambale Venkatesh, Bharath; Opdahl, Anders; Helle-Valle, Thomas M; Zareian, Mytra; Almeida, Andre L C; Choi, Eui-Young; Wu, Colin; Alonso, Alvaro; Heckbert, Susan R; Bluemke, David A; Lima, João A C

2016-08-01

Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development. © 2016 American Heart Association, Inc.

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

PubMed

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

2016-12-01

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

Metabolic Syndrome and Risk of Development of Atrial Fibrillation

PubMed Central

Watanabe, Hiroshi; Tanabe, Naohito; Watanabe, Toru; Darbar, Dawood; Roden, Dan M.; Sasaki, Shigeru; Aizawa, Yoshifusa

2008-01-01

Background The metabolic syndrome consists of a cluster of atherosclerotic risk factors, many of which also have been implicated in the genesis of atrial fibrillation (AF). However, the precise role of the metabolic syndrome in the development of AF is unknown. Methods and Results This prospective, community-based, observational cohort study was based on an annual health check-up program in Japan. We studied 28 449 participants without baseline AF. We used 2 different criteria for the metabolic syndrome—the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) and those of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI)—to study the risk of development of new-onset AF. The metabolic syndrome was present in 3716 subjects (13%) and 4544 subjects (16%) using the NCEP-ATP III and AHA/NHLBI definitions, respectively. During a mean follow-up of 4.5 years, AF developed in 265 subjects (105 women). Among the metabolic syndrome components, obesity (age- and sex-adjusted hazard ratio [HR], 1.64), elevated blood pressure (HR, 1.69), low high-density lipoprotein cholesterol (HR, 1.52), and impaired insulin tolerance (HR, 1.44 [NCEP-ATP III] and 1.35 [AHA/NHLBI]) showed an increased risk for AF. The association between the metabolic syndrome and AF remained significant in subjects without treated hypertension or diabetes by the NCEP-ATP III definition (HR, 1.78) but not by the AHA/NHLBI definition (HR, 1.28). Conclusions The metabolic syndrome was associated with increased risk of AF. The metabolic derangements of the syndrome may be important in the pathogenesis of AF. PMID:18285562

Effectiveness of structured, hospital-based, nurse-led atrial fibrillation clinics: a comparison between a real-world population and a clinical trial population.

PubMed

Qvist, Ina; Hendriks, Jeroen M L; Møller, Dorthe S; Albertsen, Andi E; Mogensen, Helle M; Oddershede, Gitte D; Odgaard, Annette; Mortensen, Leif Spange; Johnsen, Søren Paaske; Frost, Lars

2016-01-01

A previous randomised trial showed that structured, nurse-led atrial fibrillation (AF) care is superior to conventional AF care, although further research is needed to determine the outcomes of such care in a real-world setting. We compared the outcomes of patients in real-world, nurse-led, structured hospital AF clinics with the outcomes of a randomised trial of the efficacy of a nurse-led AF clinic, with respect to a composite outcome of cardiovascular-related hospitalisation and death. All patients were referred to the AF nurse specialist by cardiologists. The AF nurse specialist provided patient education, risk-factor control and stimulated empowerment and compliance. During follow-up, treatment was adjusted according to clinical guidelines. Patient education was repeated, and compliance with medical treatment was controlled. The study size was powered as a non-inferiority study. Outcome measures were adjudicated by the same principles in both cohorts. A total of 596 patients from the real world and 356 patients from a clinical trial were included in this study. No significant difference between groups with respect to age, type of AF or CHA2DS2VASc score was found. The composite primary end point occurred with an incidence rate of 8.0 (95% CI 6.1 to 10.4) per 100 person-years in the real-world population and 8.3 (95% CI 6.3 to 10.9) per 100 person-years in the clinical trial, with a crude HR of 0.83 (95% CI 0.56 to 1.23). Structured, nurse-led, hospital-based AF care appears to be effective, and patient outcomes in an actual, hospital-based, structured AF care are as least as good as those in trial settings.

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

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.

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

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

PubMed

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

2017-01-01

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

Comparison of indocyanine green fluorescence and parathyroid autofluorescence imaging in the identification of parathyroid glands during thyroidectomy.

PubMed

Kahramangil, Bora; Berber, Eren

2017-12-01

Indocyanine green fluorescence (ICGF) and parathyroid autofluorescence (AF) are two new techniques that aid in the identification of parathyroid glands (PG) intraoperatively during thyroidectomy. There is no study comparing the efficacy of these techniques. This was an IRB-approved clinical study comparing the utility of ICGF and AF for identification of PGs during thyroidectomy. Data were collected prospectively. Both techniques were compared to naked eye (NE) for PG detection. Standard statistical methods were used for data analysis. Twenty-two patients in each group underwent a total of 39 total thyroidectomies and 5 thyroid lobectomies. AF and ICGF had similar detection rates for PGs [98% (61 of 62) and 95% (60 of 63) of PGs, respectively; P=0.31]. The location of PGs was suggested before detection with NE more frequently by AF than ICGF [52% (32 of 62) vs. 6% (4 of 63) of PGs; P<0.001]. In 82% (18 of 22) of patients at least one PG was detected by AF before NE, as opposed to 14% (3 of 22) by ICGF (P<0.001). The median (range) number of PGs detected before NE per patient was greater with AF than ICGF [2 (0-3) vs. 0 (0-2)];. Upper PGs were more likely to be detected by AF before recognition with NE than the lower ones (P=0.03). There was no predictive factor for ICGF detection. Postoperative hypocalcemia rates were similar [9% (2 of 22) and 5% (1 of 22) for AF and ICGF, respectively; P>0.99]. To the best of our knowledge, this is the first comparative study between parathyroid AF and ICGF in detection of PGs during thyroidectomy. Our data suggest both techniques have similarly high detection rates and that the main difference lies in the timing of detection. AF more frequently detects PGs before recognition with NE compared to ICGF.

Comparison of indocyanine green fluorescence and parathyroid autofluorescence imaging in the identification of parathyroid glands during thyroidectomy

PubMed Central

Kahramangil, Bora

2017-01-01

Background Indocyanine green fluorescence (ICGF) and parathyroid autofluorescence (AF) are two new techniques that aid in the identification of parathyroid glands (PG) intraoperatively during thyroidectomy. There is no study comparing the efficacy of these techniques. Methods This was an IRB-approved clinical study comparing the utility of ICGF and AF for identification of PGs during thyroidectomy. Data were collected prospectively. Both techniques were compared to naked eye (NE) for PG detection. Standard statistical methods were used for data analysis. Results Twenty-two patients in each group underwent a total of 39 total thyroidectomies and 5 thyroid lobectomies. AF and ICGF had similar detection rates for PGs [98% (61 of 62) and 95% (60 of 63) of PGs, respectively; P=0.31]. The location of PGs was suggested before detection with NE more frequently by AF than ICGF [52% (32 of 62) vs. 6% (4 of 63) of PGs; P<0.001]. In 82% (18 of 22) of patients at least one PG was detected by AF before NE, as opposed to 14% (3 of 22) by ICGF (P<0.001). The median (range) number of PGs detected before NE per patient was greater with AF than ICGF [2 (0–3) vs. 0 (0–2)];. Upper PGs were more likely to be detected by AF before recognition with NE than the lower ones (P=0.03). There was no predictive factor for ICGF detection. Postoperative hypocalcemia rates were similar [9% (2 of 22) and 5% (1 of 22) for AF and ICGF, respectively; P>0.99]. Conclusions To the best of our knowledge, this is the first comparative study between parathyroid AF and ICGF in detection of PGs during thyroidectomy. Our data suggest both techniques have similarly high detection rates and that the main difference lies in the timing of detection. AF more frequently detects PGs before recognition with NE compared to ICGF. PMID:29302480

Gender, race, age, and regional differences in the association of pulse pressure with atrial fibrillation: the Reasons for Geographic and Racial Differences in Stroke study.

PubMed

Ghazi, Lama; Safford, Monika M; Khodneva, Yulia; O'Neal, Wesley T; Soliman, Elsayed Z; Glasser, Stephen P

2016-08-01

Pulse pressure (PP) has been associated with atrial fibrillation (AF) independent of other measures of arterial pressure and other AF risk factors. However, the impact of gender, race, age, and geographic region on the association between PP and AF is unclear. A cross-sectional study of data from 25,109 participants (65 ± 9 years, 54% women, 40% black) from the Reasons for Geographic and Racial Differences in Stroke study recruited between 2003 and 2007 were analyzed. AF was defined as a self-reported history of a previous physician diagnosis or presence of AF on ECG. Multivariable logistic regression models were used to calculate the odds ratio for AF. Interactions for age (<75 years and ≥75 years), gender, race, and region were examined in the multivariable adjusted model. The prevalence of AF increased with widening PP (7.9%, 7.9%, 8.4%, and 11.6%, for PP < 45, 45-54.9, 55-64.9, and ≥65 mm Hg, respectively, [P for trend <.001]) but attenuated with adjustment. No differences by gender, race, and region were observed. However, there was evidence of significant effect modification by age (interaction P = .0002). For those <75 years, PP ≥ 65 mm Hg compared to PP < 45 mm Hg was significantly associated with higher risk of AF in both the unadjusted and multivariable adjusted models (odds ratio = 1.66 [95% CI = 1.42-1.94] and 1.32 [95% CI = 1.03-1.70], respectively). In contrast, higher PP (55-64.9 mm Hg) among those ≥75 years was significantly associated with a lower risk of AF. The relationship between PP and AF may differ for older versus younger individuals. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Phytochemicals reduce aflatoxin-induced toxicity in chicken embryos.

PubMed

Yin, Hsin-Bai; Chen, Chi-Hung; Darre, Michael J; Donoghue, Ann M; Donoghue, Dan J; Venkitanarayanan, Kumar

2017-10-01

Aflatoxins (AF) are toxic metabolites produced by molds, Aspergillus flavus and Aspergillus parasiticus, which frequently contaminate poultry feed ingredients. Ingestion of AF-contaminated feed by chickens leads to deleterious effects, including decreased bird performance and reduced egg production. Moreover, AF residues in fertilized eggs result in huge economic losses by decreasing embryo viability and hatchability. This study investigated the efficacy of 2 generally recognized as safe phytochemicals, namely carvacrol (CR) and trans-cinnamaldehyde (TC), in protecting chicken embryos from AF-induced toxicity. Day-old embryonated eggs were injected with 50 ng or 75 ng AF with or without 0.1% CR or TC, followed by incubation in an incubator for 18 d. Relative embryo weight, yolk sac weight, tibia weight, tibia length, and mortality were recorded on d 18 of incubation. The effect of phytochemicals and methanol (diluent) on embryo viability was also determined. Each experiment had ten treatments with 15 eggs/treatment (n = 150 eggs/experiment) and each experiment was replicated 3 times. Both phytochemicals significantly decreased AF-induced toxicity in chicken embryos. At 75 ng of AF/egg, CR and TC increased the survival of chicken embryo by ∼55%. Moreover, CR and TC increased relative embryo weight by ∼3.3% and 17% when compared to eggs injected with 50 ng or 75 ng AF, respectively. The growth of embryos (tibia length and weight) was improved in phytochemical-treated embryos compared to those injected with AF alone (P < 0.05). Phytochemical and methanol treatments did not adversely affect embryo survival, and other measured parameters as compared to the negative control (P > 0.05). Results from this study demonstrate that CR and TC could reduce AF-induced toxicity in chicken embryos; however, additional studies are warranted to delineate the mechanistic basis behind this effect. © 2017 Poultry Science Association Inc.

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.

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.

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.

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.

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.

The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation.

PubMed

Christou, Georgios A; Christou, Konstantinos A; Korantzopoulos, Panagiotis; Rizos, Evangelos C; Nikas, Dimitrios N; Goudevenos, John A

2015-09-22

The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. A literature search based on PubMed listings was performed using "Omega-3 fatty acids" and "atrial fibrilation" as key search terms. n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions.

The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation

PubMed Central

Christou, Georgios A.; Christou, Konstantinos A.; Korantzopoulos, Panagiotis; Rizos, Evangelos C.; Nikas, Dimitrios N.; Goudevenos, John A.

2015-01-01

Background: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. Methods: A literature search based on PubMed listings was performed using “Omega-3 fatty acids” and “atrial fibrilation” as key search terms. Results: n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. Conclusions: Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions. PMID:26402674

Liver lesions produced by aflatoxins in Rana catesbeiana (bullfrog).

PubMed

Grassi, Tony Fernando; Pires, Paulo Wagner; Barbisan, Luis Fernando; Pai-Silva, Maeli Dal; Said, Roueda Abou; de Camargo, João Lauro Viana

2007-09-01

This study describes alterations induced in Rana catesbeiana (bullfrog) liver after extended dietary exposure to aflatoxins (AFs). Bullfrogs of both sexes were fed for 120 days a commercial chow blended with a rice bran-based mixture of AFs containing 667.0, 11.65, 141.74, and 3.53 mg/kg of AFs B1, B2, G1, and G2, respectively. Animals were sacrificed on study days 45, 90, and 120. Severe and progressive liver lesions with structural collapse, increased hepatocyte and biliary duct cell proliferation, appearance of basophilic hepatocytes, and diffuse scarring, were observed at all time points. There were no quantitative alterations in the liver melanomacrophage centers of the AFs-exposed animals. Increased amounts of lipid hydroperoxides, indicative of ongoing oxidative stress, were more evident in the Addutor magnum muscle than in the AFs-damaged livers. No tumors were found in the R. catesbeiana livers after 120 days of exposure to relatively high doses of AFs.

Red Wine, Resveratrol and Atrial Fibrillation.

PubMed

Stephan, Laura Siga; Almeida, Eduardo Dytz; Markoski, Melissa Medeiros; Garavaglia, Juliano; Marcadenti, Aline

2017-10-30

Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF.

Red Wine, Resveratrol and Atrial Fibrillation

PubMed Central

Garavaglia, Juliano; Marcadenti, Aline

2017-01-01

Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF. PMID:29084143

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.
.

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.

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.

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.

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.

Mineralocorticoid Receptor Antagonism in Patients With Atrial Fibrillation: Findings From the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) Registry.

PubMed

Fudim, Marat; Liu, Peter R; Shrader, Peter; Blanco, Rosalia G; Allen, Larry A; Fonarow, Gregg C; Gersh, Bernard J; Kowey, Peter R; Mahaffey, Kenneth W; Hylek, Elaine; Go, Alan S; Thomas, Laine; Peterson, Eric D; Piccini, Jonathan P

2018-04-13

Mineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes. In order to better understand MRA use and subsequent outcomes, we performed a retrospective cohort study of the contemporary ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular outcomes were compared using propensity-matched Cox proportional hazards modeling according to MRA use at baseline and new MRA use at follow-up versus patients with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were taking MRA at enrollment, and 416 patients initiated MRA use during follow-up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF. Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not associated with reduced AF progression (hazard ratio, 1.18; 95% confidence interval, 0.88-1.58; P =0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02-1.23; P =0.08). Results were similar for a comparison of new MRA users and baseline MRA users compared with nonusers. In community-based outpatients with AF, the majority of MRA use was for heart failure and hypertension. MRA use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that MRA use may decrease the risk of stroke in patients with AF. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

[Primary Study on Predicting the Termination of Paroxysmal Atrial Fibrillation Based on a Novel RdR RR Intervals Scatter Plot].

PubMed

Lu, Hongwei; Zhang, Chenxi; Sun, Ying; Hao, Zhidong; Wang, Chunfang; Tian, Jiajia

2015-08-01

Predicting the termination of paroxysmal atrial fibrillation (AF) may provide a signal to decide whether there is a need to intervene the AF timely. We proposed a novel RdR RR intervals scatter plot in our study. The abscissa of the RdR scatter plot was set to RR intervals and the ordinate was set as the difference between successive RR intervals. The RdR scatter plot includes information of RR intervals and difference between successive RR intervals, which captures more heart rate variability (HRV) information. By RdR scatter plot analysis of one minute RR intervals for 50 segments with non-terminating AF and immediately terminating AF, it was found that the points in RdR scatter plot of non-terminating AF were more decentralized than the ones of immediately terminating AF. By dividing the RdR scatter plot into uniform grids and counting the number of non-empty grids, non-terminating AF and immediately terminating AF segments were differentiated. By utilizing 49 RR intervals, for 20 segments of learning set, 17 segments were correctly detected, and for 30 segments of test set, 20 segments were detected. While utilizing 66 RR intervals, for 18 segments of learning set, 16 segments were correctly detected, and for 28 segments of test set, 20 segments were detected. The results demonstrated that during the last one minute before the termination of paroxysmal AF, the variance of the RR intervals and the difference of the neighboring two RR intervals became smaller. The termination of paroxysmal AF could be successfully predicted by utilizing the RdR scatter plot, while the predicting accuracy should be further improved.

History of hyperthyroidism and long-term outcome of catheter ablation of drug-refractory atrial fibrillation.

PubMed

Wongcharoen, Wanwarang; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Chong, Eric; Chao, Tze-Fan; Tuan, Ta-Chuan; Chang, Yao-Ting; Lin, Chin-Yu; Liao, Jo-Nan; Lin, Yi-Chun; Chen, Yun-Yu; Chen, Shih-Ann

2015-09-01

Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status. The purpose of this study was to compare the electrophysiologic characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism. The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein (PV) isolation in paroxysmal AF and additional substrate modification in nonparoxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients. Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3 ± 0.4 vs 1.0 ± 0.2, P < .01), and higher prevalence of non-PV foci (42% vs 23%, P < .01). Ectopic foci from ligament of Marshall were demonstrated more often in hyperthyroid patients (7.1% vs 1.6%, P < .01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio 2.07, 95% confidence interval 1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and those without hyperthyroid history. Patients with hyperthyroid history had a significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci compared to euthyroid patients, which resulted in a higher AF recurrence rate after a single procedure. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Pulmonary vein region ablation in experimental vagal atrial fibrillation: role of pulmonary veins versus autonomic ganglia.

PubMed

Lemola, Kristina; Chartier, Denis; Yeh, Yung-Hsin; Dubuc, Marc; Cartier, Raymond; Armour, Andrew; Ting, Michael; Sakabe, Masao; Shiroshita-Takeshita, Akiko; Comtois, Philippe; Nattel, Stanley

2008-01-29

Pulmonary vein (PV) -encircling radiofrequency ablation frequently is effective in vagal atrial fibrillation (AF), and there is evidence that PVs may be particularly prone to cholinergically induced arrhythmia mechanisms. However, PV ablation procedures also can affect intracardiac autonomic ganglia. The present study examined the relative role of PVs versus peri-PV autonomic ganglia in an experimental vagal AF model. Cholinergic AF was studied under carbachol infusion in coronary perfused canine left atrial PV preparations in vitro and with cervical vagal stimulation in vivo. Carbachol caused dose-dependent AF promotion in vitro, which was not affected by excision of all PVs. Sustained AF could be induced easily in all dogs during vagal nerve stimulation in vivo both before and after isolation of all PVs with encircling lesions created by a bipolar radiofrequency ablation clamp device. PV elimination had no effect on atrial effective refractory period or its responses to cholinergic stimulation. Autonomic ganglia were identified by bradycardic and/or tachycardic responses to high-frequency subthreshold local stimulation. Ablation of the autonomic ganglia overlying all PV ostia suppressed the effective refractory period-abbreviating and AF-promoting effects of cervical vagal stimulation, whereas ablation of only left- or right-sided PV ostial ganglia failed to suppress AF. Dominant-frequency analysis suggested that the success of ablation in suppressing vagal AF depended on the elimination of high-frequency driver regions. Intact PVs are not needed for maintenance of experimental cholinergic AF. Ablation of the autonomic ganglia at the base of the PVs suppresses vagal responses and may contribute to the effectiveness of PV-directed ablation procedures in vagal AF.

Pulmonary vein isolation combined with spironolactone or renal sympathetic denervation in patients with chronic kidney disease, uncontrolled hypertension, paroxysmal atrial fibrillation, and a pacemaker.

PubMed

Kiuchi, Márcio Galindo; Chen, Shaojie; Hoye, Neil Alexander; Pürerfellner, Helmut

2018-01-01

Atrial fibrillation (AF) commonly occurs in chronic kidney disease (CKD), occasioning adverse outcomes. Merging pulmonary vein isolation (PVI) and renal sympathetic denervation (RSD) may decrease the recurrence of AF in subjects with CKD and uncontrolled hypertension. We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity. We aimed to evaluate the impact of RSD or spironolactone 50 mg/day associated with PVI in reducing systolic blood pressure (BP), AF recurrence, and AF burden in patients with a history of paroxysmal AF and mild CKD. This was a single-center, prospective, longitudinal, randomized, double-blind study. The individuals were randomly divided into two groups (PVI + spironolactone, n = 36, and PVI + RSD, n = 33). All of them were followed for exactly 1 year to assess maintenance of sinus rhythm and to monitor the other variables. Ambulatory BP measurements were reduced in both groups and at the 12th month also differed between groups. Significantly more patients in the PVI + RSD (61%) than in the PVI + spironolactone group (36%) were AF-free at the 12th month of follow-up, P = 0.0242. Toward the end of the study, the mean AF burden was lower in the PVI + RSD group as compared to PVI + spironolactone group, at the 9th month: ∆ = - 10% (P < 0.0001), and at the 12th month: ∆ = - 12% (P < 0.0001), respectively. PVI + RSD is safe and appears to be superior to PVI + spironolactone in BP reduction, augmentation of AF event-free rate, reduction of AF burden, and improvement of renal function.

Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke.

PubMed

Johnson, Linda S B; Persson, Anders P; Wollmer, Per; Juul-Möller, Steen; Juhlin, Tord; Engström, Gunnar

2018-02-13

Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known. The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of incident AF and ischemic stroke. The population-based Malmö Diet and Cancer study includes 24-hour ECG screening of 377 AF-free individuals (mean age 64.5 years; 43% men) who were prospectively followed for >13 years. There were 65 AF events and 25 ischemic stroke events during follow-up. Subjects with an SVT episode ≥5 beats were identified, and the longest SVT episode was assessed for irregularity and lack of p waves. The association between SVT classification and AF and stroke was assessed using multivariable adjusted Cox regression. The incidence of AF increased with increasing abnormality of the SVTs. The risk-factor adjusted hazard ratio for AF was 4.95 (95% confidence interval 2.06-11.9; P <.0001) for those with short irregular SVTs (<70 beats) without p waves. The incidence of ischemic stroke was highest in the group with regular SVT episodes without p waves (hazard ratio 14.2; 95% confidence interval 3.76-57.6; P <.0001, adjusted for age and sex). Characteristics of short SVT episodes detected at 24-hour ECG screening are associated with incident AF and ischemic stroke. Short irregular SVTs without p waves likely represent early stages of AF or atrial myopathy. Twenty-four-hour ECG could identify subjects suitable for primary prevention efforts. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

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

He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediatedmore » Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.« less

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 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.

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.

Dynamic and dual-site atrial pacing in the prevention of atrial fibrillation: The STimolazione Atrial DInamica Multisito (STADIM) Study.

PubMed

De Simone, Antonio; Senatore, Gaetano; Donnici, Giovanni; Turco, Pietro; Romano, Enrico; Gazzola, Carlo; Stabile, G

2007-01-01

The impact of new algorithms to consistently pace the atrium on the prevention of atrial fibrillation (AF) remains unclear. Our randomized, crossover study compared the efficacy of single- and dual-site atrial pacing, with versus without dynamic atrial overdrive pacing in preventing AF. We studied 72 patients (mean age = 69.6 +/- 6.5 years, 34 men) with sick sinus syndrome (SSS) and paroxysmal or persistent AF, who received dual-chamber pacemakers (PM) equipped with an AF prevention algorithm and two atrial leads placed in the right atrial appendage (RAA), by passive fixation, and in the coronary sinus ostium (CS), by active fixation, respectively. At implant, the patients were randomly assigned to unipolar CS versus RAA pacing. The PM was programmed in DDDR mode 1 month after implant. Each patient underwent four study phases of equal duration: (1) unipolar, single site (CS or RAA) pacing with the AF algorithm ON (atrial lower rate = 0 ppm); (2) unipolar, single site pacing with the AF algorithm OFF (atrial lower rate = 70 bpm); (3) bipolar, dual-site pacing with AF algorithm ON; (4) bipolar, dual-site pacing with the AF algorithm OFF. Among 40 patients (56%), who completed the follow-up (15 +/- 4 months) no difference was observed in the mean number of automatic mode switch (AMS) corrected for the duration of follow-up, in unipolar (5.6 +/- 22.8 vs 2.6 +/- 5.5) or bipolar mode (3.3 +/- 12.7 vs 2.1 +/- 4.9) with, respectively, the algorithm OFF or ON. With the AF prevention algorithm ON, the percentage of atrial pacing increased significantly from 78.7 +/- 22.1% to 92.4 +/- 4.9% (P < 0.001), while the average ventricular heart rate was significantly lower with the algorithm ON (62.4 +/- 17.5 vs 79.9 +/- 3 bpm (P < 0.001). The AF prevention algorithm increased the percentage of atrial pacing significantly, regardless of the atrial pulse configuration and pacing site, while maintaining a slower ventricular heart rate. It had no impact on the number of AMS in the unipolar and bipolar modes in patients with SSS.

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.

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

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.

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.

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.

Radiofrequency Catheter Ablation Improves the Quality of Life Measured with a Short Form-36 Questionnaire in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis

PubMed Central

Choi, Jong-Il; Kim, Young-Hoon

2016-01-01

Background The main purpose of performing radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients is to improve the quality of life (QoL) and alleviate AF-related symptoms. We aimed to determine the qualitative and quantitative effects of RFCA on the QoL in AF patients. Methods We performed a systemic review and meta-analysis using a random effects model. We searched for the studies that reported the physical component summary score (PCS) and mental component summary score (MCS) of the short form-36, a validated system to assess and quantify the QoL, before and after RFCA in AF patients. PCS and MCS are T-scores with a mean of 50 and standard deviation of 10. Results Of the 470 studies identified through systematic search, we included 13 studies for pre-RFCA vs. the post-RFCA analysis and 5 studies for treatment success vs. AF recurrence analyses. In the pre-RFCA vs. post-RFCA analysis, RFCA was associated with a significant increase in both the PCS (weighted mean difference [WMD] = 6.33 [4.81–7.84]; p < 0.001) and MCS (WMD = 7.80 [6.15–9.44]; p < 0.001). The ΔPCS (post-RFCA PCS–pre-RFCA PCS) and ΔMCS values were used for the treatment success vs. AF recurrence analysis. Patients with successful ablation had a higher ΔPCS (WMD = 7.46 [4.44–10.49]; p < 0.001) and ΔMCS (WMD = 7.59 [4.94–10.24]; p < 0.001). Conclusions RFCA is associated with a significant increase in the PCS and MCS in AF patients. Patients without AF recurrence after RFCA had a better improvement in the PCS and MCS than patients who had AF recurrence. PMID:27681507

Physical activity is associated with a reduced risk of atrial fibrillation in middle-aged and elderly women.

PubMed

Drca, Nikola; Wolk, Alicja; Jensen-Urstad, Mats; Larsson, Susanna C

2015-10-01

Previous studies have found that regular participation in intense physical activity increases the risk of developing atrial fibrillation (AF) in men, but it remains unclear how physical activity influences the risk of AF in women. We aimed to examine whether physical activity of different types and at different ages influences the development of AF in women. In the population-based Swedish Mammography Cohort, information about physical activity was obtained from 36 513 AF-free women (49-83 years old, median age 60 years) who had completed a questionnaire at study entry (1997). Participants reported their time spent on leisure-time exercise and on walking or bicycling throughout their lifetime (at study entry, and at 30 and 50 years of age). We used the Swedish National Inpatient Register (IPR) to determine whether the participants were diagnosed with AF. Cox proportional hazards regression models were used to estimate relative risks (RR) with 95% CI, adjusted for potential confounders. During a median follow-up of 12 years (10th percentile 7.5 years, 90th percentile 12.0 years), 2915 cases of AF were diagnosed. The risk of AF decreased with increasing levels of leisure-time exercise at study entry (RR 0.85, 95% CI 0.75 to 0.95 for ≥4 h/week vs <1 h/week) and walking/bicycling (RR 0.81, 95% CI 0.72 to 0.92, for ≥40 min/day vs almost never). Physical activity is associated with a reduced risk of AF in women. Moderate amount of physical activity was sufficient to significantly reduce AF risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

PubMed Central

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

2015-01-01

Introduction Postoperative atrial fibrillation (AF) occurs in 30–40% of patients after cardiac surgery. Identification of recurrent postoperative AF is required to initiate evidence-based management to reduce the risk of subsequent stroke. However, as AF is often asymptomatic, recurrences may not be detected after discharge. This study determines feasibility and impact of a self-surveillance programme to identify recurrence of postoperative AF in the month of posthospital discharge. Methods and analysis This is a feasibility study, using a cross-sectional study design, of self-screening for AF using a hand-held single-lead iPhone electrocardiograph device (iECG). Participants will be recruited from the cardiothoracic surgery wards of the Royal North Shore Hospital and North Shore Private Hospital, Sydney, Australia. Cardiac surgery patients admitted in sinus rhythm and experiencing a transient episode of postoperative AF will be eligible for recruitment. Participants will be taught to take daily ECG recordings for 1 month posthospital discharge using the iECG and will be provided education regarding AF, including symptoms and health risks. The primary outcome is the feasibility of patient self-monitoring for AF recurrence using an iECG. Secondary outcomes include proportion of patients identified with recurrent AF; estimation of stroke risk and patient knowledge. Process outcomes and qualitative data related to acceptability of patient's use of the iECG and sustainability of the screening programme beyond the trial setting will also be collected. Ethics and dissemination Primary ethics approval was received on 25 February 2014 from Northern Sydney Local Health District Human Resource Ethics Committee, and on 17 July 2014 from North Shore Private Hospital Ethics Committee. Results will be disseminated via forums including, but not limited to, peer-reviewed publications and presentation at national and international conferences. Trial registration number ACTRN12614000383662. PMID:25586373

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

PubMed

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

2015-01-13

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

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

Stepanyuk, Galina A.; Serrano, Pedro; Peralta, Eigen

RNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional co-activator of estrogen receptors and Jun/AP-1, and its function has been associated with malignant progression in a number of cancers. The C-terminal RRM domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein–protein interactions through a short tryptophan-containing peptide known as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are reported. The RBM39–U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, by isothermal titration calorimetry and by NMR chemicalmore » shift perturbation experiments with the purified proteins. When compared with related complexes, such as U2AF35–U2AF65 and RBM39–SF3b155, the RBM39-UHM–U2AF65-ULM complex reveals both common and discriminating recognition elements in the UHM–ULM binding interface, providing a rationale for the known specificity of UHM–ULM interactions. This study therefore establishes a structural basis for specific UHM–ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells.« less

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

NASA Technical Reports Server (NTRS)

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

2015-01-01

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

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.

The prognostic significance of atrial fibrillation in heart failure with preserved ejection function: insights from KaRen, a prospective and multicenter study.

PubMed

Bosseau, Christian; Donal, Erwan; Lund, Lars H; Oger, Emmanuel; Hage, Camilla; Mulak, Geneviève; Daubert, Jean-Claude; Linde, Cecilia

2017-06-01

The prognostic value of atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFPEF) remains controversial. We sought to study the prognostic value of AF in a prospective cohort and to characterize the HFPEF patients with AF. KaRen was a prospective, multicenter, international, observational study intended to characterize HFPEF; 538 patients presenting with an acute decompensated cardiac failure and a left ventricular EF > 45% were included. EKG and echocardiogram performed 4-8 week following the index hospitalization were analyzed in core centers. Clinical and echocardiographic characteristics of patients in sinus rhythm vs. with documented AF at enrolment (decompensated HF), upon their 4-8-week visit (in presumed stable clinical condition) and according to patients' cardiac history, were compared. The primary study endpoint was death from any cause or first hospitalization for decompensated heart failure (HF). A total of 413 patients (32% in AF) were analyzed, with a mean follow-up period of 28 months. The patients were primarily elderly individuals (mean age: 76.2 years), with a slight female predominance and a high prevalence of non-cardiovascular comorbidities. The baseline echocardiographic characteristics and the natriuretic peptide levels were indicative of a more severe heart condition among the patients with AF. However, the patients with AF exhibited a similar survival-free interval compared with the patients in sinus rhythm. In this elderly HFPEF population with a high prevalence of non-cardiovascular comorbidities, the presence of AF was not associated with a worse prognosis despite impaired clinical and echocardiographic features.ClinicalTrials.gov: NCT00774709.

Management of atrial fibrillation: focus on the role of dronedarone.

PubMed

Cheng, Judy Wm

2011-01-01

Dronedarone is an amiodarone derivative that was approved in the US in July 2009 to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF), who are in sinus rhythm (SR), or who will be cardioverted. This article reviews the pharmacology, adverse effects, and clinical evidence available to date on the use of dronedarone in the management of AF and its potential role in the emergency department setting. In the EURIDIS and ADONIS studies evaluating the efficacy of dronedarone in maintaining SR, dronedarone significantly reduced the risk of recurrence of AF compared to placebo, by 22% and 27%, respectively. The ERATO study examined the ability of dronedarone to control ventricular rate in permanent AF. The DIONYSOS study demonstrated that recurrences of AF were more frequent with dronedarone. However, discontinuation of therapy due to intolerance was more frequent with amiodarone. Furthermore, the ATHENA study demonstrated that dronedarone reduced mortality and cardiovascular hospitalization by 24% (P < 0.05) in patients in SR but with other associated risks and a history of AF. However, the ANDROMEDA study, evaluating the use of dronedarone in patients with recent decompensated heart failure, and the PALLAS study, evaluating the use of dronedarone in patients with chronic AF, were both terminated prematurely due to a trend toward an increased risk of cardiovascular events. Dronedarone has been demonstrated to be effective in reducing the incidence of AF recurrence. It appears to be less effective but better tolerated than amiodarone. Dronedarone appears to have a low proarrhythmic risk and is the first anti-arrhythmic that has been demonstrated to reduce cardiovascular mortality and cardiovascular hospitalization in clinically stable patients with other risk factors for recurrent AF. Therefore, dronedarone can be recommended as an anti-arrhythmic of choice in clinically stable patients for maintaining SR. If dronedarone is to be used in a patient with chronic stable heart failure, the patient must be monitored closely for any worsening of heart failure symptoms. The drug must be discontinued should the heart failure symptoms worsen.

Acute Exposure to Air Pollution Triggers Atrial Fibrillation

PubMed Central

Link, Mark S.; Luttmann-Gibson, Heike; Schwartz, Joel; Mittleman, Murray A.; Wessler, Benjamin; Gold, Diane R.; Dockery, Douglas W.; Laden, Francine

2013-01-01

Objective The aim of the present study is to evaluate the association of air pollution with the onset of atrial fibrillation (AF). Background Air pollution in general and more specifically particulate matter has been associated with cardiovascular events. Although ventricular arrhythmias are traditionally thought to convey the increased cardiovascular risk, AF may also contribute. Methods Patients with dual chamber implantable cardioverter defibrillators (ICDs) were enrolled and followed prospectively. The association of AF onset with air quality including ambient PM2.5, black carbon, sulfate, particle number, NO2, SO2, and O3 in the 24 hours prior to the arrhythmia was examined utilizing a case-crossover analysis. In sensitivity analyses, associations with air pollution between 2 and 48 hours prior to the AF were examined. Results Of 176 patients followed for an average of 1.9 years, 49 patients had 328 episodes of AF lasting ≥ 30 seconds. Positive but nonsignificant associations were found for PM2.5 in the prior 24 hours, but stronger associations were found with shorter exposure windows. The odds of AF increased by 26% (95% CI 8% to 47%) for each 6.0 µg/m3 increase in PM2.5 in the 2 hours prior to the event (p=0.004). The odds of AF was highest at the upper quartile of mean PM2.5. Conclusion Particulate matter was associated with increased odds of AF onset within hours following exposure in patients with known cardiac disease. Air pollution is an acute trigger of AF, likely contributing to the pollution-associated adverse cardiac outcomes observed in epidemiological studies. PMID:23770178

In vitro antineoplastic effects of auranofin in canine lymphoma cells.

PubMed

Zhang, Hong; Rose, Barbara J; Pyuen, Alex A; Thamm, Douglas H

2018-05-03

The orally available gold complex auranofin (AF) has been used in humans, primarily as an antirheumatic/immunomodulatory agent. It has been safely administered to healthy dogs to establish pharmacokinetic parameters for oral administration, and has also been used as a treatment in some dogs with immune-mediated conditions. Multiple in vitro studies have recently suggested that AF may possess antineoplastic properties. Spontaneous canine lymphoma may be a very useful translational model for the study of human lymphoma, prompting the evaluation of AF in canine lymphoma cells. We investigated the antineoplastic activity of AF in 4 canine lymphoid tumor derived cell lines through measurements of proliferation, apoptosis, thioredoxin reductase (TrxR) activity and generation of reactive oxygen species (ROS), and detected the effects of AF when combined with conventional cytotoxic drugs using the Chou and Talalay method. We also evaluated the antiproliferative effects of AF in primary canine lymphoma cells using a bioreductive fluorometric assay. At concentrations that appear clinically achievable in humans, AF demonstrated potent antiproliferative and proapoptotic effects in canine lymphoid tumor cell lines. TrxR inhibition and increased ROS production was observed following AF treatment. Moreover, a synergistic antiproliferative effect was observed when AF was combined with lomustine or doxorubicin. Auranofin appears to inhibit the growth and initiate apoptosis in canine lymphoma cells in vitro at clinically achievable concentrations. Therefore, this agent has the potential to have near-term benefit for the treatment of canine lymphoma, as well as a translational model for human lymphoma. Decreased TrxR activity and increasing ROS production may be useful biomarkers of drug exposure.

Racial and Ethnic Differences in the Prevalence, Management and Outcomes in Patients with Atrial Fibrillation: A Systematic Review.

PubMed

Ugowe, Francis E; Jackson, Larry R; Thomas, Kevin L

2018-05-23

Atrial Fibrillation (AF) is the most common cardiac arrhythmia in the United States (US) and is associated with increased morbidity, mortality, and healthcare expenditures. In this work, our aim was to assess for racial and ethnic differences in the epidemiology, management and outcomes of patients with AF. A search of relevant studies from January 1, 2007 to December 30, 2017 was conducted using PubMed, EMBASE, and Web of Science and supplemented by manual searches of the bibliographies of retrieved articles. We identified 152 studies of which 64 were subsequently included. We found underrepresented racial and ethnic groups (UREGs) have a higher prevalence of established risk factors associated with the development of AF, but an overall lower incidence and prevalence of AF compared with non-Hispanic whites (NHW). Moreover, racial and ethnic differences exist in detection, awareness and AF-associated symptoms. Non-white populations also experience decreased use of rhythm control modalities and anticoagulation for stroke prevention. Lastly, among those with AF, UREGs suffer increased morbidity and mortality relative to white groups. Racial and ethnic differences exist in the prevalence, quality of life, management and outcomes of individuals with AF; however, the mechanisms for these differences have yet to be fully elucidated. Racial and ethnic differences in AF warrant further analysis to understand the factors contributing to the differences in prevalence and management to ensure the delivery of high quality care that prevents stroke, reduces deaths and decreases expenses associated with caring for underrepresented populations with AF. Copyright © 2018. Published by Elsevier Inc.

The Associations of Atrial Fibrillation With the Risks of Incident Invasive Breast and Colorectal Cancer

PubMed Central

Wassertheil-Smoller, Sylvia; McGinn, Aileen P.; Martin, Lisa; Rodriguez, Beatriz L.; Stefanick, Marcia L.; Perez, Marco

2017-01-01

Abstract Atrial fibrillation (AF) is a common arrhythmia that poses a significant risk of stroke. Cross-sectional and case-control studies have shown evidence of associations between AF and breast or colorectal cancer, but there have been no longitudinal studies in which this has been assessed. We prospectively examined a cohort of 93,676 postmenopausal women enrolled in the Women's Health Initiative from 1994 to 1998 to determine whether there are relationships between baseline AF and the development of invasive breast or colorectal cancer. The prevalence of self-reported physician diagnosis of AF at baseline was 5.1%. Over approximately 15 years of follow-up, the incidence of invasive breast cancer was 5.7%, and the incidence of colorectal cancer was 1.6%. Adjusted hazard ratios and 95% confidence intervals were obtained using Cox proportional hazards models. We found no significant association between AF and incident colorectal cancer, but we did see a 19% excess risk of invasive breast cancer among those with AF (adjusted hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.03, 1.38). Additional adjustment for baseline use of cardiac glycosides attenuated the association between AF and invasive breast cancer (HR = 1.01, 95% CI: 0.85, 1.20). Cardiac glycoside use was strongly associated with incident invasive breast cancer (HR = 1.68, 95% CI: 1.33, 2.12) independent of AF and other confounders. Mechanisms of the associations among breast cancer, AF, and cardiac glycosides need further investigation. PMID:28174828

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

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.

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

ERIC Educational Resources Information Center

Walsh, Desmond; And Others

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

Adherence to treatment guidelines: the association between stroke risk stratified comparing CHADS2 and CHA2DS2-VASc score levels and warfarin prescription for adult patients with atrial fibrillation.

PubMed

Chapman, Scott A; St Hill, Catherine A; Little, Meg M; Swanoski, Michael T; Scheiner, Shellina R; Ware, Kenric B; Lutfiyya, M Nawal

2017-02-11

Ischemic stroke is a risk associated with atrial fibrillation (AF) and is estimated to occur five times more often in afflicted patients than in those without AF. Anti-thrombotic therapy is recommended for the prevention of ischemic stroke. Risk stratification tools, such as the CHADS 2 , and more recently the CHA 2 DS 2 -VASc, for predicting stroke in patients with AF have been developed to determine the level of stroke risk and assist clinicians in the selection of antithrombotic therapy. Warfarin, for stroke prevention in AF, is the most commonly prescribed anticoagulant in North America. The purpose of this study was to examine the utility of using the CHADS 2 score levels (low and high) in contrast to the CHA 2 DS 2 -VASc when examining the outcome of warfarin prescriptions for adult patients with AF. The CHA 2 DS 2 -VASc tool was not widely used in 2010, when the data analyzed were collected. It has only been since 2014 that CHA 2 DS 2 -VASc criteria has been recommended to guide anticoagulant treatment in updated AF treatment guidelines. Bivariate and multivariate data analysis strategies were used to analyze 2010 National Ambulatory Care Survey (NAMCS) data. NAMCS is designed to collect data on the use and provision of ambulatory care services nationwide. The study population for this research was US adults with a diagnosis of AF. Warfarin prescription was the dependent variable for this study. The study population was 7,669,844 AF patients. Bivariate analysis revealed that of those AF patients with a high CHADS 2 score, 25.1% had received a warfarin prescription and 18.8 for those with a high CHA 2 DS 2 -VASc score. Logistic regression analysis yielded that patients with AF had higher odds of having a warfarin prescription if they had a high CHADS 2 score, were Caucasian, lived in a zip code where < 20% of the population had a university education, and lived in a zip code where < 10% of the population were living in households with incomes below the federal poverty level. Further, the analysis yielded that patients with AF had lesser odds of having a warfarin prescription if they were ≥ 65 years of age, female, or had health insurance. Overall, warfarin appears to be under-prescribed for patients with AF regardless of the risk stratification system used. Based on the key findings of our study opportunities for interventions are present to improve guideline adherence in alignment with risk stratification for stroke prevention. Interprofessional health care teams can provide improved medical management of stroke prevention for patients with AF. These interprofessional health care teams should be constituted of primary care providers (physicians, physician assistants, and nurse practitioners), nurses (RN, LPN), and pharmacists (PharmD, RPh).

Genetic Variants Related to Height and Risk of Atrial Fibrillation

PubMed Central

Rosenberg, Michael A.; Kaplan, Robert C.; Siscovick, David S.; Psaty, Bruce M.; Heckbert, Susan R.; Newton-Cheh, Christopher; Mukamal, Kenneth J.

2014-01-01

Increased height is a known independent risk factor for atrial fibrillation (AF). However, whether genetic determinants of height influence risk is uncertain. In this candidate gene study, we examined the association of 209 height-associated single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of European descent from the Cardiovascular Health Study, a prospective cohort study of older adults (aged ≥65 years) enrolled in 1989–1990. After a median follow-up period of 13.2 years, 879 participants developed incident AF. The height-associated SNPs together explained approximately 10% of the variation in height (P = 6.0 × 10−8). Using an unweighted genetic height score, we found a nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95% confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that genetically predicted height was strongly associated with AF risk (per 10 cm, hazard ratio = 1.30, 95% confidence interval: 1.03, 1.64; P = 0.03). Importantly, for all models, the inclusion of actual height completely attenuated the genetic height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was independently associated with AF and may warrant future study. In conclusion, we found that genetic determinants of height appear to increase the risk of AF, primarily via height itself. This approach of examining SNPs associated with an intermediate phenotype should be considered as a method for identifying novel genetic targets. PMID:24944287

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

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.

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.

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 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.

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.

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.

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.

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.

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

Ablation for Atrial Fibrillation

PubMed Central

2006-01-01

Executive Summary Objective To review the effectiveness, safety, and costing of ablation methods to manage atrial fibrillation (AF). The ablation methods reviewed were catheter ablation and surgical ablation. Clinical Need Atrial fibrillation is characterized by an irregular, usually rapid, heart rate that limits the ability of the atria to pump blood effectively to the ventricles. Atrial fibrillation can be a primary diagnosis or it may be associated with other diseases, such as high blood pressure, abnormal heart muscle function, chronic lung diseases, and coronary heart disease. The most common symptom of AF is palpitations. Symptoms caused by decreased blood flow include dizziness, fatigue, and shortness of breath. Some patients with AF do not experience any symptoms. According to United States data, the incidence of AF increases with age, with a prevalence of 1 per 200 people aged between 50 and 60 years, and 1 per 10 people aged over 80 years. In 2004, the Institute for Clinical Evaluative Sciences (ICES) estimated that the rate of hospitalization for AF in Canada was 582.7 per 100,000 population. They also reported that of the patients discharged alive, 2.7% were readmitted within 1 year for stroke. One United States prevalence study of AF indicated that the overall prevalence of AF was 0.95%. When the results of this study were extrapolated to the population of Ontario, the prevalence of AF in Ontario is 98,758 for residents aged over 20 years. Currently, the first-line therapy for AF is medical therapy with antiarrhythmic drugs (AADs). There are several AADs available, because there is no one AAD that is effective for all patients. The AADs have critical adverse effects that can aggravate existing arrhythmias. The drug selection process frequently involves trial and error until the patient’s symptoms subside. The Technology Ablation has been frequently described as a “cure” for AF, compared with drug therapy, which controls AF but does not cure it. Ablation involves directing an energy source at cardiac tissue. For instance, radiofrequency energy uses heat to burn tissue near the source of the arrhythmia. The purpose is to create a series of scar tissue, so that the aberrant electrical pathways can no longer exist. Because the pulmonary veins are the predominant source of AF initiation, the primary goal of ablation is to isolate the pulmonary veins from the left atria through the creation of a conduction block. There are 2 methods of ablation: catheter ablation and surgical (operative) ablation. Radiofrequency energy is most commonly used for ablation. Catheter ablation involves inserting a catheter through the femoral vein to access the heart and burn abnormal foci of electrical activity by direct contact or by isolating them from the rest of the atrium. The surgical ablation is performed minimally invasively via direct visualization or with the assistance of a special scope for patients with lone AF. Review Strategy In March 2006, the following databases were searched: Cochrane Library International Agency for Health Technology Assessment (first quarter 2006), Cochrane Database of Systematic Reviews (first quarter 2006), Cochrane Central Register of Controlled Trials (first quarter 2006), MEDLINE (1966 to February 2006), MEDLINE In-Process and Other Non-indexed Citations (1966 to March 1, 2006), and EMBASE (1980 to 2006 week 9). The Medical Advisory Secretariat also searched Medscape on the Internet for recent reports on trials that were unpublished but that were presented at international conferences. In addition, the Web site Current Controlled Trials (www.controlled-trials.com) was searched for ongoing trials investigating ablation for atrial fibrillation. Search terms included: radiofrequency ablation, catheter ablation and atrial fibrillation. Summary of Findings Sixteen RCTs were identified that compared ablation methods in patients with AF. Two studies were identified that investigated first-line therapy for AF or atrial flutter. Seven other studies examined patients with drug-refractory, lone AF; and the remaining 7 RCTs compared ablation plus heart surgery to heart surgery alone in patients with drug-refractory AF and concomitant heart conditions. First-line Catheter Ablation for Atrial Fibrillation or Atrial Flutter Both studies concluded that catheter ablation was associated with significantly improved long-term freedom from arrhythmias and quality of life compared with medical therapy. These studies included different patient populations (those with AF in one pilot study, and those with atrial flutter in the other). Catheter ablation as first-line treatment is considered experimental at this time. Catheter Ablation Versus Medical Therapy in Patients With Drug-Refractory, Lone Atrial Fibrillation In this review, catheter ablation had success rates (freedom from arrhythmia) that ranged from 42% to 90% (median, 74%) in patients with drug-refractory, lone AF. All 3 of the RCTs comparing catheter ablation to medical therapy in patients with drug-refractory, lone AF found a significant improvement in terms of freedom from arrhythmia over a minimum of 12 months follow-up (P<.05). Ablation Plus Heart Surgery Versus Heart Surgery Alone in Patients With Atrial Fibrillation It is clear that patients with drug-refractory AF who are undergoing concomitant heart surgery (usually mitral valve repair or replacement) benefit significantly from surgical ablation, in terms of long-term freedom from AF, without substantial additional risk compared to open heart surgery alone. This group of patients represents about 1% of the patients with atrial fibrillation, thus the majority of the burden of AF lies within the patients with lone AF (i.e. those not requiring additional heart surgery). Conclusion Catheter ablation appears to be an effective treatment for patients with drug-refractory AF whose treatment alternatives are limited. Ablation technology is continually evolving with increasing success rates associated with the ablation procedure. PMID:23074498

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.

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.

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.

Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

PubMed Central

Benjamin, Emelia J.; Rice, Kenneth M.; Arking, Dan E.; Pfeufer, Arne; van Noord, Charlotte; Smith, Albert V.; Schnabel, Renate B.; Bis, Joshua C.; Boerwinkle, Eric; Sinner, Moritz F.; Dehghan, Abbas; Lubitz, Steven A.; D’Agostino, Ralph B.; Lumley, Thomas; Ehret, Georg B.; Heeringa, Jan; Aspelund, Thor; Newton-Cheh, Christopher; Larson, Martin G.; Marciante, Kristin D.; Soliman, Elsayed Z.; Rivadeneira, Fernando; Wang, Thomas J.; Eiriksdottir, Gudny; Levy, Daniel; Psaty, Bruce M.; Li, Man; Chamberlain, Alanna M.; Hofman, Albert; Vasan, Ramachandran S.; Harris, Tamara B.; Rotter, Jerome I.; Kao, W.H. Linda; Agarwal, Sunil K.; Ch. Stricker, Bruno H.; Wang, Ke; Launer, Lenore J.; Smith, Nicholas L.; Chakravarti, Aravinda; Uitterlinden, Andre G.; Wolf, Philip A; Sotoodehnia, Nona; Kottgen, Anna; van Duijn, Cornelia M.; Lunetta, Kathryn L.; Heckbert, Susan R.; Gudnason, Vilmundur; Alonso, Alvaro; Kaab, Stefan; Ellinor, Patrick T.; Witteman, Jacqueline C.

2009-01-01

We conducted meta-analyses of genome-wide association studies (GWAS) for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a novel locus for AF (ZFHX3, rs2106261, risk ratio [RR]=1.19; P=2.3×10−7), an association that was replicated in the German AF Network (odds ratio=1.44; P=1.6×10−11). Combining the discovery and replication results, rs2106261 was significantly associated with AF (RR=1.25; P=1.8×10−15). PMID:19597492

Student Perspectives on Assessment for Learning

ERIC Educational Resources Information Center

DeLuca, Christopher; Chapman-Chin, Allison E. A.; LaPointe-McEwan, Danielle; Klinger, Don A.

2018-01-01

Assessment for learning (AfL) has become a widespread approach across many educational systems. To date, AfL research has emphasized teachers' knowledge, skills, and practices, with few studies examining students' responses to an AfL pedagogical approach. The purpose of this research was to focus directly on students' perspectives on their use and…

Effect of Incorporating Adaptive Functioning Scores on the Prevalence of Intellectual Disability

ERIC Educational Resources Information Center

Obi, Obianuju; Braun, Kim Van Naarden; Baio, Jon; Drews-Botsch, Carolyn; Devine, Owen; Yeargin-Allsopp, Marshalyn

2011-01-01

Surveillance and epidemiologic research on intellectual disability often do not incorporate adaptive functioning (AF) data. Exclusion of AF data leads to overestimation of the prevalence of intellectual disability, the extent of which is not known. In this study, the authors evaluated the effect of incorporating AF data on overall intellectual…

A Longitudinal Study of Maternal Interactional Styles and Infant Visualization.

ERIC Educational Resources Information Center

Saxon, Terrill F.; And Others

1997-01-01

Examined interactional and attentional relationships in 65 mother-infant dyads (infants at ages 6 and 8 months), focusing on attention following (AF), attention switching (AS), and joint attention. Found that AF and AS were unrelated at 6 months but inversely related at 8 months. AF and AS were unrelated to joint attention. (MDM)

Interaction of actin filaments with the plasma membrane in Amoeba proteus: studies using a cell model and isolated plasma membrane.

PubMed

Kawakatsu, T; Kikuchi, A; Shimmen, T; Sonobe, S

2000-08-01

We prepared a cell model of Amoeba proteus by mechanical bursting to study the interaction between actin filaments (AFs) and plasma membrane (PM). The cell model prepared in the absence of Ca2+ showed remarkable contraction upon addition of ATP. When the model was prepared in the presence of Ca2+, the cytoplasmic granules formed an aggregate in the central region, having moved away from PM. Although this model showed contraction upon addition of ATP in the presence of Ca2+, less contraction was noted. Staining with rhodamine-phalloidin revealed association of AFs with PM in the former model, and a lesser amount of association in the latter model. The interaction between AFs and PM was also studied using the isolated PM. AFs were associated with PM isolated in the absence of Ca2+, but were not when Ca2+ was present. These results suggest that the interaction between AFs and PM is regulated by Ca2+.

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.

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.

[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.

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.

Right Ventricular Structure and Function Are Associated With Incident Atrial Fibrillation: MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right Ventricle).

PubMed

Chatterjee, Neal A; Shah, Ravi V; Murthy, Venkatesh L; Praestgaard, Amy; Shah, Sanjiv J; Ventetuolo, Corey E; Barr, R Graham; Kronmal, Richard; Lima, Joao A C; Bluemke, David A; Jerosch-Herold, Michael; Alonso, Alvaro; Kawut, Steven M

2017-01-01

Right ventricular (RV) morphology has been associated with drivers of atrial fibrillation (AF) risk, including left ventricular and pulmonary pathology, systemic inflammation, and neurohormonal activation. The aim of this study was to investigate the association between RV morphology and risk of incident AF. We interpreted cardiac magnetic resonance imaging in 4204 participants free of clinical cardiovascular disease in the MESA (Multi-Ethnic Study of Atherosclerosis). Incident AF was determined using hospital discharge records, study electrocardiograms, and Medicare claims data. The study sample (n=3819) was 61±10 years old and 47% male with 47.2% current/former smokers. After adjustment for demographics and clinical factors, including incident heart failure, higher RV ejection fraction (hazard ratio, 1.16 per SD; 95% confidence interval, 1.03-1.32; P=0.02) and greater RV mass (hazard ratio, 1.25 per SD; 95% confidence interval, 1.08-1.44; P=0.002) were significantly associated with incident AF. After additional adjustment for the respective left ventricular parameter, higher RV ejection fraction remained significantly associated with incident AF (hazard ratio, 1.15 per SD; 95% confidence interval, 1.01-1.32; P=0.04), whereas the association was attenuated for RV mass (hazard ratio, 1.16 per SD; 95% confidence interval, 0.99-1.35; P=0.07). In a subset of patients with available spirometry (n=2540), higher RV ejection fraction and mass remained significantly associated with incident AF after additional adjustment for lung function (P=0.02 for both). Higher RV ejection fraction and greater RV mass were associated with an increased risk of AF in a multiethnic population free of clinical cardiovascular disease at baseline. © 2017 American Heart Association, Inc.

Compromised redox homeostasis, altered nitroso–redox balance, and therapeutic possibilities in atrial fibrillation

PubMed Central

Simon, Jillian N.; Ziberna, Klemen; Casadei, Barbara

2016-01-01

Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso–redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF. PMID:26786158

Ultracold Realization of AntiFerromagenteic Order

NASA Astrophysics Data System (ADS)

Shrestha, Uttam

2011-03-01

We investigate numerically the experimental feasibility of observing the antiferromagnetic (AF) order in the bosonic mixtures of rubidium (87 Rb) and potassium (41 K) in a two-dimensional optical lattice with external trapping potential. Within the mean-field approximation we have found the ground states which, for a specific range of parameters such as inter-species interactions and lattice height, interpolate from phase separation to the AF order. For the moderate lattice heights the coexistence of the Mott and AF phase is possible for rubidium atoms while the potassium atoms remain superfluid with overlapped AF phase. In our view there has not been any study on AF order in two-component systems when one component remains in the superfluid phase while the other is in the Mott phase. Therefore, this observation may provide a novel regime for studying quantum magnetism in ultracold systems. This work was supported by the EU Contract EU STREP NAMEQUAM.

Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults.

PubMed

Hussein, Ayman A; Bartz, Traci M; Gottdiener, John S; Sotoodehnia, Nona; Heckbert, Susan R; Lloyd-Jones, Donald; Kizer, Jorge R; Christenson, Robert; Wazni, Oussama; deFilippi, Christopher

2015-05-01

Various mechanisms in cardiac remodeling related to atrial fibrillation (AF) lead to elevated circulating cardiac troponin levels, but little is known about such elevations upstream to AF onset. The purpose of this study was to study the association between circulating troponin levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and incident atrial fibrillation (AF). In a large prospective cohort of ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels were measured in sera that were collected at enrollment from 4262 participants without AF (2871 with follow-up measurements). Incident AF was identified by electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare files, including outpatient and physician claims diagnoses. Over median follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0%) developed AF. Higher baseline levels of hs-cTnT were associated with incident AF in covariate-adjusted analyses accounting for demographics, traditional risk factors, and incident heart failure in time-dependent analyzes (hazard ratio for 3rd tertile vs undetectable 1.75, 95% confidence interval 1.48-2.08). This association was statistically significant in analyses that additionally adjusted for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd tertile vs undetectable 1.38, 95% confidence interval 1.16-1.65). Significant associations were also found when hs-cTnT levels were treated as a continuous variable and when examining change from baseline of hs-cTnT levels and incident AF. The findings show a significant association of circulating troponin levels in ambulatory older adults with incident AF beyond that of traditional risk factors, incident heart failure, and biomarkers of inflammation and hemodynamic strain. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Atrial fibrillation and cognitive decline-the role of subclinical cerebral infarcts: the atherosclerosis risk in communities study.

PubMed

Chen, Lin Y; Lopez, Faye L; Gottesman, Rebecca F; Huxley, Rachel R; Agarwal, Sunil K; Loehr, Laura; Mosley, Thomas; Alonso, Alvaro

2014-09-01

The mechanism underlying the association of atrial fibrillation (AF) with cognitive decline in stroke-free individuals is unclear. We examined the association of incident AF with cognitive decline in stroke-free individuals, stratified by subclinical cerebral infarcts (SCIs) on brain MRI scans. We analyzed data from 935 stroke-free participants (mean age±SD, 61.5±4.3 years; 62% women; and 51% black) from 1993 to 1995 through 2004 to 2006 in the Atherosclerosis Risk in Communities Study, a biracial community-based prospective cohort study. Cognitive testing (including the digit symbol substitution and the word fluency tests) was performed in 1993 to 1995, 1996 to 1998, and 2004 to 2006 and brain MRI scans in 1993 to 1995 and 2004 to 2006. During follow-up, there were 48 incident AF events. Incident AF was associated with greater annual average rate of decline in digit symbol substitution (-0.77; 95% confidence interval, -1.55 to 0.01; P=0.054) and word fluency (-0.80; 95% confidence interval, -1.60 to -0.01; P=0.048). Among participants without SCIs on brain MRI scans, incident AF was not associated with cognitive decline. In contrast, incident AF was associated with greater annual average rate of decline in word fluency (-2.65; 95% confidence interval, -4.26 to -1.03; P=0.002) among participants with prevalent SCIs in 1993 to 1995. Among participants who developed SCIs during follow-up, incident AF was associated with a greater annual average rate of decline in digit symbol substitution (-1.51; 95% confidence interval, -3.02 to -0.01; P=0.049). The association of incident AF with cognitive decline in stroke-free individuals can be explained by the presence or development of SCIs, raising the possibility of anticoagulation as a strategy to prevent cognitive decline in AF. © 2014 American Heart Association, Inc.

Quantitative fundus autofluorescence in mice: correlation with HPLC quantitation of RPE lipofuscin and measurement of retina outer nuclear layer thickness.

PubMed

Sparrow, Janet R; Blonska, Anna; Flynn, Erin; Duncker, Tobias; Greenberg, Jonathan P; Secondi, Roberta; Ueda, Keiko; Delori, François C

2013-04-17

Our study was conducted to establish procedures and protocols for quantitative autofluorescence (qAF) measurements in mice, and to report changes in qAF, A2E bisretinoid concentration, and outer nuclear layer (ONL) thickness in mice of different genotypes and age. Fundus autofluorescence (AF) images (55° lens, 488 nm excitation) were acquired in albino Abca4(-/-), Abca4(+/-), and Abca4(+/+) mice (ages 2-12 months) with a confocal scanning laser ophthalmoscope (cSLO). Gray levels (GLs) in each image were calibrated to an internal fluorescence reference. The bisretinoid A2E was measured by quantitative high performance liquid chromatography (HPLC). Histometric analysis of ONL thicknesses was performed. The Bland-Altman coefficient of repeatability (95% confidence interval) was ±18% for between-session qAF measurements. Mean qAF values increased with age (2-12 months) in all groups of mice. qAF was approximately 2-fold higher in Abca4(-/-) mice than in Abca4(+/+) mice and approximately 20% higher in heterozygous mice. HPLC measurements of the lipofuscin fluorophore A2E also revealed age-associated increases, and the fold difference between Abca4(-/-) and wild-type mice was more pronounced (approximately 3-4-fold) than measurable by qAF. Moreover, A2E levels declined after 8 months of age, a change not observed with qAF. The decline in A2E levels in the Abca4(-/-) mice corresponded to reduced photoreceptor cell viability as reflected in ONL thinning beginning at 8 months of age. The qAF method enables measurement of in vivo lipofuscin and the detection of genotype and age-associated differences. The use of this approach has the potential to aid in understanding retinal disease processes and will facilitate preclinical studies.

Relevance of Conduction Disorders in Bachmann's Bundle During Sinus Rhythm in Humans.

PubMed

Teuwen, Christophe P; Yaksh, Ameeta; Lanters, Eva A H; Kik, Charles; van der Does, Lisette J M E; Knops, Paul; Taverne, Yannick J H J; van de Woestijne, Pieter C; Oei, Frans B S; Bekkers, Jos A; Bogers, Ad J J C; Allessie, Maurits A; de Groot, Natasja M S

2016-05-01

Bachmann's bundle (BB) is considered to be the main route of interatrial conduction and to play a role in development of atrial fibrillation (AF). The goals of this study are to characterize the presence of conduction disorders in BB during sinus rhythm and to study their relation with AF. High-resolution epicardial mapping (192 unipolar electrodes, interelectrode distance: 2 mm) of sinus rhythm was performed in 185 patients during coronary artery bypass surgery of whom 13 had a history of paroxysmal AF. Continuous rhythm monitoring was used to detect postoperative AF during the first 5 postoperative days. In 67% of the patients, BB was activated from right to left; in the remaining patients from right and middle (21%), right, central, and left (8%), or central (4%) site. Mean effective conduction velocity was 89 cm/s. Conduction block was present in most patients (75%; median 1.1%, range 0-12.8) and was higher in patients with paroxysmal AF compared with patients without a history of AF (3.2% versus 0.9%; P=0.03). A high amount of conduction block (>4%) was associated with de novo postoperative AF (P=0.02). Longitudinal lines of conduction block >10 mm were also associated with postoperative AF (P=0.04). BB may be activated through multiple directions, but the predominant route of conduction is from right to left. Conduction velocity across BB is around 90 cm/s. Conduction is blocked in both longitudinal and transverse direction in the majority of patients. Conduction disorders, particularly long lines of longitudinal conduction block, are more pronounced in patients with AF episodes. © 2016 American Heart Association, Inc.

Role of fetal sex in amniotic fluid alphafetoprotein screening.

PubMed

Knippel, Alexander Johannes

2002-10-01

Previous studies have shown that fetal gender has influence on various pregnancy complications and prenatal diagnostic biochemical markers. We have evaluated, whether elevation of amniotic fluid alphafetoprotein (AF AFP) is associated with fetal sex and whether a sex-related difference can help to identify pregnancies with AFP-associated malformations or fetal loss. From our database we obtained 6461 singleton gestations with AF AFP measurements for the period April 1997-March 1999. Patients with AF AFP >1.9 MoM were identified, details of pregnancy outcome were obtained and compared to matched-pair controls having AF AFP <2 MoM. In 232 of 262 patients having AF AFP levels >1.9 MoM outcome information was available. Of these fetuses, significantly more had male gender (147 male fetuses versus 85 female). Having a screen-positive result the risk of AFP-associated malformations was significantly higher for female fetuses (25 female fetuses (29.4%) versus 22 male fetuses (15%) with AFP-associated malformations). Adjusting the cut-off MoM to 2.5 for male and to 2.0 for female fetuses halves the false positive rate from 3.4 to 1.7% without affecting the detection rate of 95%. Pregnancies with false positive AF AFP had a significantly higher risk for fetal loss compared with pregnancies having normal AF AFP (ten fetal losses from 185 versus two fetal losses from 232), but fetal gender had no significant influence. Adjusting AF AFP MoM cut-offs for fetal gender could increase performance of AF-AFP screening. Larger studies are required to determine suitable sex-adjusted cut-off levels. Copyright 2002 John Wiley & Sons, Ltd.

Identification of active atrial fibrillation sources and their discrimination from passive rotors using electrographical flow mapping.

PubMed

Bellmann, Barbara; Lin, Tina; Ruppersberg, Peter; Zettwitz, Marit; Guttmann, Selma; Tscholl, Verena; Nagel, Patrick; Roser, Mattias; Landmesser, Ulf; Rillig, Andreas

2018-05-09

The optimal ablation approach for the treatment of persistent atrial fibrillation (AF) is still under debate; however, the identification and elimination of AF sources is thought to play a key role. Currently available technologies for the identification of AF sources are not able to differentiate between active rotors or focal impulse (FI) and passive circular turbulences as generated by the interaction of a wave front with a functional obstacle such as fibrotic tissue. This study introduces electrographic flow (EGF) mapping as a novel technology for the identification and characterization of AF sources in humans. Twenty-five patients with AF (persistent: n = 24, long-standing persistent: n = 1; mean age 70.0 ± 8.3 years, male: n = 17) were included in this prospective study. Focal impulse and Rotor-Mapping (FIRM) was performed in addition to pulmonary vein isolation using radiofrequency in conjunction with a 3D-mapping-system. One-minute epochs were exported from the EP-recording-system and re-analyzed using EGF mapping after the procedure. 44 potential AF sources (43 rotors and one FI) were identified with FIRM and 39 of these rotors were targeted for ablation. EGF mapping verified 40 of these patterns and identified 24/40 (60%) as active sources while 16/40 (40%) were classified as passive circular turbulences. Four rotors were not identified by EGF mapping. EGF is the first method to identify active AF sources during AF ablation procedures in humans and discriminate them from passive rotational phenomena, which occur if the excitation wavefront passes conduction bariers. EGF mapping may allow improved guidance of AF ablation procedures.

Association between hepatic steatosis and serum liver enzyme levels with atrial fibrillation in the general population: The Study of Health in Pomerania (SHIP).

PubMed

Markus, Marcello Ricardo Paulista; Meffert, Peter J; Baumeister, Sebastian Edgar; Lieb, Wolfgang; Siewert, Ulrike; Schipf, Sabine; Koch, Manja; Kors, Jan A; Felix, Stephan Burkhard; Dörr, Marcus; Targher, Giovanni; Völzke, Henry

2016-02-01

Hepatic steatosis (HS) affects up to 35% of adults in the general population. Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and has a substantial impact on healthcare costs. We analyzed cross-sectional associations of HS and serum liver enzyme levels with prevalent AF in a general population sample. We analyzed data from 3090 women and men, aged 20-81 years, from the population-based Study of Health in Pomerania. HS was determined by ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) were measured photometrically. AF was determined by automatic electrocardiographic analysis software. The prevalences of HS and AF were 30.3% and 1.49%, respectively. ALT, AST and GGT showed a positive linear association with the risk of prevalent AF, after multivariable adjustment. The adjusted odds ratios for AF per 1-standard deviation increment in log-transformed serum liver enzyme levels were 1.65 (95% confidence interval [CI]: 1.16 to 2.35; p = 0.006) for ALT, 1.47 (95%CI: 1.07 to 2.02; p = 0.017) for AST and 2.17 (95%CI: 1.64 to 2.87; p < 0.001) for GGT. In contrast, ultrasonographic HS was not associated with AF. Our findings indicate that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population. The hepatic release of increased levels of serum liver enzymes might be accompanied by higher levels of pro-inflammatory, pro-coagulant and pro-fibronogenic mediators that might lead to structural and electrical remodeling of the atrium resulting in the development and persistence of AF. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Acute exposure to air pollution triggers atrial fibrillation.

PubMed

Link, Mark S; Luttmann-Gibson, Heike; Schwartz, Joel; Mittleman, Murray A; Wessler, Benjamin; Gold, Diane R; Dockery, Douglas W; Laden, Francine

2013-08-27

This study sought to evaluate the association of air pollution with the onset of atrial fibrillation (AF). Air pollution in general and more specifically particulate matter has been associated with cardiovascular events. Although ventricular arrhythmias are traditionally thought to convey the increased cardiovascular risk, AF may also contribute. Patients with dual chamber implantable cardioverter-defibrillators (ICDs) were enrolled and followed prospectively. The association of AF onset with air quality including ambient particulate matter <2.5 μm aerodynamic diameter (PM2.5), black carbon, sulfate, particle number, NO2, SO2, and O3 in the 24 h prior to the arrhythmia was examined utilizing a case-crossover analysis. In sensitivity analyses, associations with air pollution between 2 and 48 h prior to the AF were examined. Of 176 patients followed for an average of 1.9 years, 49 patients had 328 episodes of AF lasting ≥ 30 s. Positive but nonsignificant associations were found for PM2.5 in the prior 24 h, but stronger associations were found with shorter exposure windows. The odds of AF increased by 26% (95% confidence interval: 8% to 47%) for each 6.0 μg/m(3) increase in PM2.5 in the 2 h prior to the event (p = 0.004). The odds of AF were highest at the upper quartile of mean PM2.5. PM was associated with increased odds of AF onset within hours following exposure in patients with known cardiac disease. Air pollution is an acute trigger of AF, likely contributing to the pollution-associated adverse cardiac outcomes observed in epidemiological studies. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort

PubMed Central

Son, Mi Kyoung; Lim, Nam-Kyoo; Kim, Hyung Woo

2017-01-01

Atrial fibrillation (AF) is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old) without previous stroke who were diagnosed with AF in 2007–2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6%) patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients) associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32–0.53). Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days) continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed. PMID:28636620

Inappropriate combination of warfarin and aspirin.

PubMed

Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

2016-03-01

A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

Second trimester amniotic fluid glucose, uric acid, phosphate, potassium, and sodium concentrations in relation to maternal pre-pregnancy BMI and birth weight centiles.

PubMed

Fotiou, Maria; Michaelidou, Alexandra Maria; Athanasiadis, Apostolos P; Menexes, Georgios; Symeonidou, Maria; Koulourida, Vasiliki; Ganidou, Maria; Theodoridis, Theodoros D; Tarlatzis, Basil C

2015-05-01

To study the evolution profile of amniotic fluid (AF) glucose, uric acid, phosphate, potassium, and sodium, in the second trimester of pregnancy, and explore the possible relations between the concentration of these components and maternal, as well as neonatal characteristics. AF of 52 pregnant women was analyzed using an automatic multichannel analyzer. Maternal age, pre-pregnancy Body Mass Index (BMI), inter-pregnancy intervals, and smoking status were derived from questionnaires. Information on pregnancy and delivery was collected from medical records. Uric acid increased (r = 0.423, p < 0.01), while phosphate and glucose concentrations decreased during the period of 16-26th week of pregnancy (r = -0.590, p < 0.001 and r = -0.314, p < 0.05, respectively). Maternal pre-pregnancy BMI was significantly correlated with AF uric acid concentration (r = 0.460, p < 0.01) and marginally with AF glucose (r = 0.274, p = 0.052) and sodium (r = 0.254, p = 0.070) levels. Multiple linear regression indicated that mid-trimester AF uric acid and phosphate levels were significantly related to birth weight centiles (R(2)( )= 0.345, p < 0.05). Our results suggest that: (a) AF phosphate levels reflect gestational age to a satisfactory extent, (b) maternal pre-pregnancy BMI is significantly correlated with AF uric acid concentration, and (c) in appropriate for gestational age infants, AF phosphate and uric acid levels may serve as potential biomarkers of birth weight centiles. Further studies on AF composition may help to unravel the biochemical pathways underlying fetal development and could offer insight on the potential impact of maternal nutritional management on fetal growth regulation.

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

PubMed

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

2015-03-01

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

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway.

PubMed

Liu, Guang-Zhong; Hou, Ting-Ting; Yuan, Yue; Hang, Peng-Zhou; Zhao, Jing-Jing; Sun, Li; Zhao, Guan-Qi; Zhao, Jing; Dong, Jing-Mei; Wang, Xiao-Bing; Shi, Hang; Liu, Yong-Wu; Zhou, Jing-Hua; Dong, Zeng-Xiang; Liu, Yang; Zhan, Cheng-Chuang; Li, Yue; Li, Wei-Min

2016-03-01

Atrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action. The expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min(-1) for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed. The PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF. Fenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF. © 2016 The British Pharmacological Society.

Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension.

PubMed

Milazzo, Valeria; Maule, Simona; Di Stefano, Cristina; Tosello, Francesco; Totaro, Silvia; Veglio, Franco; Milan, Alberto

2015-12-01

Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m(2), P=0.59) and carotid-femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four-hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. © 2015 American Heart Association, Inc.

Biomarkers of Atrial Cardiopathy and Atrial Fibrillation Detection on Mobile Outpatient Continuous Telemetry After Embolic Stroke of Undetermined Source.

PubMed

Sebasigari, Denise; Merkler, Alexander; Guo, Yang; Gialdini, Gino; Kummer, Benjamin; Hemendinger, Morgan; Song, Christopher; Chu, Antony; Cutting, Shawna; Silver, Brian; Elkind, Mitchell S V; Kamel, Hooman; Furie, Karen L; Yaghi, Shadi

2017-06-01

Biomarkers of atrial dysfunction or "cardiopathy" are associated with embolic stroke risk. However, it is unclear if this risk is mediated by undiagnosed paroxysmal atrial fibrillation or flutter (AF). We aim to determine whether atrial cardiopathy biomarkers predict AF on continuous heart-rhythm monitoring after embolic stroke of undetermined source (ESUS). This was a single-center retrospective study including all patients with ESUS undergoing 30 days of ambulatory heart-rhythm monitoring to look for AF between January 1, 2013 and December 31, 2015. We reviewed medical records for clinical, radiographic, and cardiac variables. The primary outcome was a new diagnosis of AF detected during heart-rhythm monitoring. The primary predictors were atrial biomarkers: left atrial diameter on echocardiography, P-wave terminal force in electrocardiogram (ECG) lead V1, and P wave - R wave (PR) interval on ECG. A multiple logistic regression model was used to assess the relationship between atrial biomarkers and AF detection. Among 196 eligible patients, 23 (11.7%) were diagnosed with AF. In unadjusted analyses, patients with AF were older (72.4 years versus 61.4 years, P < .001) and had larger left atrial diameter (39.2 mm versus 35.7 mm, P = .03). In a multivariable model, the only predictor of AF was age ≥ 60 years (odds ratio, 3.0; 95% CI, 1.06-8.5; P = .04). Atrial biomarkers were weakly associated with AF after ESUS. This suggests that previously reported associations between these markers and stroke may reflect independent cardiac pathways leading to stroke. Prospective studies are needed to investigate these mechanisms. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes.

PubMed

Matern, Andreas; Pedrolli, Danielle; Großhennig, Stephanie; Johansson, Jörgen; Mack, Matthias

2016-12-01

The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B 2 ), RoF, and AF in the human pathogen Listeria monocytogenes, a bacterium which is a riboflavin auxotroph. We show that the L. monocytogenes protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. Lmo1329 generates the cofactors flavin mononucleotide (FMN) and FAD, whereas Lmo0728 produces FAD only. The combined activities of Lmo1329 and Lmo0728 are responsible for the intracellular formation of the toxic cofactor analogs roseoflavin mononucleotide (RoFMN), roseoflavin adenine dinucleotide (RoFAD), 8-demethyl-8-aminoriboflavin mononucleotide (AFMN), and 8-demethyl-8-aminoriboflavin adenine dinucleotide (AFAD). In vivo reporter gene assays and in vitro transcription/translation experiments show that the L. monocytogenes FMN riboswitch Rli96, which controls expression of the riboflavin transport gene lmo1945, is negatively affected by riboflavin/FMN and RoF/RoFMN but not by AF/AFMN. Treatment of L. monocytogenes with RoF or AF leads to drastically reduced FMN/FAD levels. We suggest that the reduced flavin cofactor levels in combination with concomitant synthesis of inactive cofactor analogs (RoFMN, RoFAD, AFMN, and AFAD) explain why RoF and AF contribute to antibiotic activity in L. monocytogenes IMPORTANCE: The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are small molecules which are produced by Streptomyces davawensis and Streptomyces cinnabarinus RoF and AF were reported to have antibacterial activity, and we studied how these compounds are metabolized by the human bacterial pathogen Listeria monocytogenes We found that the L. monocytogenes protein Lmo1945 mediates uptake of AF and RoF and that the combined activities of the enzymes Lmo1329 and Lmo0728 are responsible for the conversion of AF and RoF to toxic cofactor analogs. Comparative studies with RoF and AF (a weaker antibiotic) suggest that the reduction in FMN/FAD levels and the formation of inactive FMN/FAD analogs explain to a large extent the antibiotic activity of AF and RoF. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Occupational physical activity, but not leisure-time physical activity increases the risk of atrial fibrillation: The Copenhagen City Heart Study.

PubMed

Skielboe, Ane K; Marott, Jacob L; Dixen, Ulrik; Friberg, Jens B; Jensen, Gorm B

2016-11-01

Previous findings regarding physical activity and risk of incident atrial fibrillation (AF) are controversial, focusing on leisure-time physical activity (LTPA) and without distinguishing it from occupational physical activity (OPA). Our aim was to study the association between physical activity and risk of AF, with special attention to the possible divergent effects of OPA and LTPA. In a prospective, observational cohort study, 17,196 subjects were included from the Copenhagen Population Register. All participants had a physical examination, a 12-lead electrocardiogram (ECG), and answered a questionnaire regarding health and physical activity. Participants without previously diagnosed AF who answered adequately regarding OPA and LTPA were included. LTPA and OPA were each graded into four levels. Follow-up were carried out between 1981-1983, 1991-1994, and 2001-2003. Information regarding hospitalization and mortality was drawn from the National Patient Registry and the Registry of Causes of Death. Outcome was incident AF as determined by follow-up ECG or register diagnosis. In univariable Cox regression analysis all sub-groups of OPA had a significant higher risk of AF compared to moderate OPA. When adjusting for confounders, the risk remained significantly increased for high OPA (hazard ratio (HR) 1.21 (95% confidence interval (CI) 1.02-1.43), p = 0.028), and very high OPA (HR 1.39 (95% CI 1.03-1.88), p = 0.034). We found no significant association between LTPA and incident AF. High and very high OPA were associated with a significantly increased risk of incident AF. LTPA was not associated with risk of incident AF. © The European Society of Cardiology 2016.

EARLY: a pilot study on early diagnosis of atrial fibrillation in a primary healthcare centre.

PubMed

Benito, Luisa; Coll-Vinent, Blanca; Gómez, Eva; Martí, David; Mitjavila, Joan; Torres, Ferran; Miró, Òscar; Sisó, Antoni; Mont, Lluís

2015-11-01

Atrial fibrillation (AF) is associated with high morbidity and mortality. Early diagnosis is likely to improve therapy and prognosis. The study objective was to evaluate the usefulness of a programme for early diagnosis of AF in patients from an urban primary care centre. Participants were recruited from a randomized sample of patients not diagnosed with AF but having relevant risk factors: age ≥ 65 years, ischaemic and/or valvular heart disease, congestive heart failure, hypertension, and/or diabetes. Patients were randomly assigned to the intervention group (IG) or control group (CG). The intervention included (i) initial visit with clinical history, electrocardiogram, and instruction about pulse palpation and warning signs and (ii) electrocardiogram every 6 months during a 2-year follow-up. The main endpoint of the study was the proportion of new cases diagnosed at 6 months. Secondary endpoints were number of new AF diagnoses and complications associated with the arrhythmia in both groups. A total of 928 patients were included (463 IG and 465 CG). At 6 months, AF was diagnosed in 8 IG patients and 1 CG patient (1.7 vs. 0.2%, respectively, P = 0.018). After 2 years of follow-up, 11 IG patients and 6 CG patients had newly diagnosed AF (2.5 vs. 1.3%, respectively, P = 0.132). Time to first diagnosis of AF was shorter in IG patients [median (inter-quartile range): 7 (192) days vs. 227 (188.5) days in CG, P = 0.029]. The simple screening proposed could be useful for the early detection of AF in primary care. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Human amniotic fluid-derived mesenchymal stem cells as therapeutic vehicles: a novel approach for the treatment of bladder cancer.

PubMed

Bitsika, Vasiliki; Roubelakis, Maria G; Zagoura, Dimitra; Trohatou, Ourania; Makridakis, Manousos; Pappa, Kalliopi I; Marini, Frank C; Vlahou, Antonia; Anagnou, Nicholas P

2012-05-01

Recent studies support cell-based therapies for cancer treatment. An advantageous cell type for such therapeutic schemes are the mesenchymal stem cells (MSCs) that can be easily propagated in culture, genetically modified to express therapeutic proteins, and exhibit an innate tropism to solid tumors in vivo. Recently, we successfully isolated and expanded MSCs from second-trimester amniotic fluid (AF-MSCs). The main characteristic of AF-MSCs is their efficient and rapid expansion in vitro. Herein, we investigated the AF-MSCs tropism and capability to transport interferon beta (IFNβ) to the region of neoplasia in a bladder tumor model. To this end, we used the T24M bladder cancer cell line, previously generated from our studies, and developed a disease progression model in immunosuppressed mice, that can recapitulate the molecular events of bladder carcinogenesis. Our results documented that AF-MSCs exhibited high motility, when migrated either to T24M cells or to T24M-conditioned medium, and we further identified and studied the secreted factors which may trigger these enhanced migratory properties. Further, lentivirus-transduced AF-MSCs, expressing green fluorescent protein (GFP) or IFNβ, were intravenously administered to T24M tumor-bearing animals at multiple doses to examine their therapeutic effect. GFP- and IFNβ-AF-MSCs successfully migrated and colonized at the tumor site. Notably, significant inhibition of tumor growth as well as prolonged survival of mice were observed in the presence of IFNβ-AF-MSCs. Collectively, these results document the great potential of AF-MSCs as anti-cancer vehicles, implemented by the targeting of the tumor site and further facilitated by their high proliferation rate and expansion efficiency in culture.

Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants.

PubMed

Pancholy, Samir B; Sharma, Parikshit S; Pancholy, Dipti S; Patel, Tejas M; Callans, David J; Marchlinski, Francis E

2014-02-01

Studies comparing gender-specific outcomes in patients with atrial fibrillation (AF) have reported conflicting results. Gender differences in cerebrovascular accident/systemic embolism (CVA/SE) or major bleeding outcomes with novel oral anticoagulant (NOAC) use are not known. The goal of this analysis was to perform a systematic review and meta-analysis evaluating gender differences in residual risk of CVA/SE and major bleeding outcomes in patients with nonvalvular AF treated with either warfarin or NOAC. Sixty-four randomized studies were identified using keywords "gender," "AF," and "CVA." Using the Preferred Reporting Items for Systemic Reviews and Meta-analysis method, 6 studies met criteria for inclusion in this meta-analysis. CVA/SE and major bleeding outcomes were separately analyzed in cohorts receiving warfarin and NOAC agents, comparing men with women. Women with AF taking warfarin were at a significantly greater residual risk of CVA/SE compared with men (odds ratio 1.279, 95% confidence interval 1.111 to 1.473, Z = -3.428, p = 0.001). No gender difference in residual risk of CVA/SE was noted in patients with AF receiving NOAC agents (odds ratio 1.146, 95% confidence interval 0.97 to 1.354, p = 0.109). Major bleeding was less frequent in women with AF treated with NOAC. In conclusion, women with AF treated with warfarin have a greater residual risk of CVA/SE and an equivalent major bleeding risk, whereas those treated with NOAC agents deemed superior to warfarin are at equivalent residual risk of CVA/SE and less major bleeding risk compared with men. These results suggest an increased net clinical benefit of NOAC agents compared with warfarin in treating women with AF. Copyright © 2014 Elsevier Inc. All rights reserved.

Alignment-free microbial phylogenomics under scenarios of sequence divergence, genome rearrangement and lateral genetic transfer.

PubMed

Bernard, Guillaume; Chan, Cheong Xin; Ragan, Mark A

2016-07-01

Alignment-free (AF) approaches have recently been highlighted as alternatives to methods based on multiple sequence alignment in phylogenetic inference. However, the sensitivity of AF methods to genome-scale evolutionary scenarios is little known. Here, using simulated microbial genome data we systematically assess the sensitivity of nine AF methods to three important evolutionary scenarios: sequence divergence, lateral genetic transfer (LGT) and genome rearrangement. Among these, AF methods are most sensitive to the extent of sequence divergence, less sensitive to low and moderate frequencies of LGT, and most robust against genome rearrangement. We describe the application of AF methods to three well-studied empirical genome datasets, and introduce a new application of the jackknife to assess node support. Our results demonstrate that AF phylogenomics is computationally scalable to multi-genome data and can generate biologically meaningful phylogenies and insights into microbial evolution.

Light-Irradiation Wavelength and Intensity Changes Influence Aflatoxin Synthesis in Fungi

PubMed Central

Suzuki, Tadahiro

2018-01-01

Fungi respond to light irradiation by forming conidia and occasionally synthesizing mycotoxins. Several light wavelengths, such as blue and red, affect the latter. However, the relationship between light irradiation and mycotoxin synthesis varies depending on the fungal species or strain. This study focused on aflatoxin (AF), which is a mycotoxin, and the types of light irradiation that increase AF synthesis. Light-irradiation tests using the visible region indicated that blue wavelengths in the lower 500 nm region promoted AF synthesis. In contrast, red wavelengths of 660 nm resulted in limited significant changes compared with dark conditions. Irradiation tests with different intensity levels indicated that a low light intensity increased AF synthesis. For one fungal strain, light irradiation decreased the AF synthesis under all wavelength conditions. However, the decrease was mitigated by 525 nm low intensity irradiation. Thus, blue-green low intensity irradiation may increase AF synthesis in fungi. PMID:29304012

Obesity and Atrial Fibrillation Prevalence, Pathogenesis, and Prognosis: Effects of Weight Loss and Exercise.

PubMed

Lavie, Carl J; Pandey, Ambarish; Lau, Dennis H; Alpert, Martin A; Sanders, Prashanthan

2017-10-17

Both obesity and atrial fibrillation (AF) are increasing in epidemic proportions, and both increase the prevalence of cardiovascular disease events. Obesity has adverse effects on cardiovascular hemodynamics and cardiac structure and function, and increases the prevalence of AF, partly related to electroanatomic remodeling in obese patients. However, numerous studies, including in AF, have demonstrated an obesity paradox, where overweight and obese patients with these disorders have a better prognosis than do leaner patients with the same degree of severity of cardiovascular disease/AF. In this paper, the authors discuss special issues regarding AF in obesity, as well as the evidence that despite the presence of an obesity paradox, there are benefits of weight loss, physical activity/exercise training, and increases in cardiorespiratory fitness on the prognosis of obese patients with AF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Causes and Predictors of Readmission in Patients With Atrial Fibrillation Undergoing Catheter Ablation: A National Population-Based Cohort Study.

PubMed

Arora, Shilpkumar; Lahewala, Sopan; Tripathi, Byomesh; Mehta, Varshil; Kumar, Varun; Chandramohan, Divya; Lemor, Alejandro; Dave, Mihir; Patel, Nileshkumar; Patel, Nilay V; Palamaner Subash Shantha, Ghanshyam; Viles-Gonzalez, Juan; Deshmukh, Abhishek

2018-06-15

Reducing readmission after catheter ablation (CA) in atrial fibrillation (AF) is important. We utilized National Readmission Data (NRD) 2010-2014. AF was identified by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnostic code 427.31 in the primary field, while first CA of AF was identified via ICD-9 -procedure code 37.34. Any admission within 30 or 90 days of index admission was considered a readmission. Cox proportional hazard regression was used to adjust for confounders. The primary outcomes were 30- and 90-day readmissions and the secondary outcome was AF recurrence. In total, 1 128 372 patients with AF were identified from January 1, 2010 to September 30, 2014. Of which 37 360 (3.3%) underwent CA. Patients aged ≥65 years and female sex were less likely to receive CA for AF. Overall, 10.9% and 16.5% of CA patients were readmitted within 30 and 90 days post-CA, respectively. Most common causes of readmissions were arrhythmia (AF, atrial flutter), heart failure, pulmonary causes (pneumonia, chronic obstructive pulmonary disease) and bleeding complications (gastrointestinal bleed, intracranial hemorrhage). Patients with diabetes mellitus, heart failure, coronary artery disease (CAD), chronic pulmonary and kidney disease, prior stroke/transient ischemic attack (TIA), female sex, length of stay ≥2 and disposition to the facility were prone to higher 30- and 90-day readmissions post-CA. Predictors of increase in AF recurrence post-CA were female sex, diabetes mellitus, chronic pulmonary disease, and length of stay ≥2. Trends of 90-day readmission and AF recurrence were found to improve over the study period. We identified several demographic and clinical factors associated with the use of CA in AF, and short-term outcomes of the same, which could potentially help in the patient selection and improve outcomes. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

PubMed Central

RUSSO, VINCENZO; DI MEO, FEDERICA; PAPA, ANDREA ANTONIO; CIOPPA, NADIA DELLA; PROIETTI, RICCARDO; RUSSO, MARIA GIOVANNA; CALABRÒ, RAFFAELE; POLITANO, LUISA

2014-01-01

P-wave dispersion is a non invasive indicator of intra-atrial conduction heterogeneity producing substrate for reentry, which is a pathophysiological mechanism of atrial fibrillation. The relationship between P-wave dispersion (PD) and atrial fibrillation (AF) in Myotonic dystrophy type 1 (DM1) patients is still unclear. Atrial Preference Pacing (APP) is an efficient algorithm to prevent paroxysmal AF in patients implanted with dual-chamber pacemaker. Aim of our study was to evaluate the possible correlation between atrial preference pacing algorithm, P-wave dispersion and AF burden in DM1 patients with normal cardiac function underwent permanent dual-chamber pacemaker implantation. We enrolled 50 patients with DM1 (age 50.3 ± 7.3; 11 F) underwent dual-chamber pacemaker implantation for various degree of atrioventricula block. The study population was randomized following 1 months stabilization period to APP algorithm features programmed OFF or ON. Patients were assessed every 3 months for the first year, and every 6 months thereafter up to 3 years. At each follow-up visit, we counted: the number of premature atrial beats, the number and the mean duration of AF episodes, AF burden and the percentage of atrial and ventricular pacing. APP ON Group showed lower number of AF episodes (117 ± 25 vs. 143 ± 37; p = 0.03) and AF burden (3059 ± 275 vs. 9010 ± 630 min; p < 0.04) than APP OFF Group. Atrial premature beats count (44903 ± 30689 vs. 13720 ± 7717 beats; p = 0.005) and Pwave dispersion values (42,1 ± 11 ms vs. 29,1 ± 4,2 ms, p = 0,003) were decreased in APP ON Group. We found a significant positive correlation between PD and AF burden (R = 0,8, p = 0.007). Atrial preference pacing algorithm, decreasing the number of atrial premature beats and the P-wave dispersion, reduces the onset and perpetuator factors of AF episodes and decreases the AF burden in DM1 patients underwent dual chamber pacemaker implantation for various degree of atrioventricular blocks and documented atrial fibrillation. PMID:25873781

Diagnostic Accuracy of a Novel Mobile Phone Application for the Detection and Monitoring of Atrial Fibrillation.

PubMed

Rozen, Guy; Vaid, Jeena; Hosseini, Seyed Mohammadreza; Kaadan, M Ihsan; Rafael, Allon; Roka, Attila; Poh, Yukkee C; Poh, Ming-Zher; Heist, Edwin Kevin; Ruskin, Jeremy Neil

2018-05-15

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, associated with significant morbidity, increased mortality, and rising health-care costs. Simple and available tools for the accurate detection of arrhythmia recurrence in patients after electrical cardioversion (CV) or ablation procedures for AF can help to guide therapeutic decisions. We conducted a prospective, single-center study to evaluate the accuracy of Cardiio Rhythm Mobile Application (CRMA) for AF detection. Patients >18 years of age who were scheduled for elective CV for AF were enrolled in the study. CRMA finger pulse recordings, utilizing an iPhone camera, were obtained before (pre-CV) and after (post-CV) the CV. The findings were validated against surface electrocardiograms. Ninety-eight patients (75.5% men), mean age of 67.7 ± 10.5 years, were enrolled. No electrocardiogram for validation was available in 1 case. Pre-CV CRMA readings were analyzed in 97 of the 98 patients. Post-CV CRMA readings were analyzed for 92 of 93 patients who underwent CV. One patient left before the recording was obtained. The Cardiio Rhythm Mobile Application correctly identified 94 of 101 AF recordings (93.1%) as AF and 80 of 88 non-AF recordings (90.1%) as non-AF. The sensitivity was 93.1% (95% confidence interval [CI] = 86.9% to 97.2%) and the specificity was 90.9% (95% CI = 82.9% to 96.0%). The positive predictive value was 92.2% (95% CI = 85.8% to 95.8%) and the negative predictive value was 92.0% (95% CI = 94.8% to 95.9%). In conclusion, the CRMA demonstrates promising potential in accurate detection and discrimination of AF from normal sinus rhythm in patients with a history of AF. Copyright © 2018 Elsevier Inc. All rights reserved.

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.

PubMed

Baumgartner, Christine; da Costa, Bruno R; Collet, Tinh-Hai; Feller, Martin; Floriani, Carmen; Bauer, Douglas C; Cappola, Anne R; Heckbert, Susan R; Ceresini, Graziano; Gussekloo, Jacobijn; den Elzen, Wendy P J; Peeters, Robin P; Luben, Robert; Völzke, Henry; Dörr, Marcus; Walsh, John P; Bremner, Alexandra; Iacoviello, Massimo; Macfarlane, Peter; Heeringa, Jan; Stott, David J; Westendorp, Rudi G J; Khaw, Kay-Tee; Magnani, Jared W; Aujesky, Drahomir; Rodondi, Nicolas

2017-11-28

Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. © 2017 American Heart Association, Inc.

Left Atrial Appendage Electrical Isolation and Concomitant Device Occlusion to Treat Persistent Atrial Fibrillation: A First-in-Human Safety, Feasibility, and Efficacy Study.

PubMed

Panikker, Sandeep; Jarman, Julian W E; Virmani, Renu; Kutys, Robert; Haldar, Shouvik; Lim, Eric; Butcher, Charles; Khan, Habib; Mantziari, Lilian; Nicol, Edward; Foran, John P; Markides, Vias; Wong, Tom

2016-07-01

Left atrial appendage (LAA) electric isolation is reported to improve persistent atrial fibrillation (AF) ablation outcomes. However, loss of LAA mechanical function may increase thromboembolic risk. Concomitant LAA electric isolation and occlusion as part of conventional AF ablation has never been tested in humans. We therefore evaluated the feasibility, safety, and efficacy of LAA electric isolation and occlusion in patients undergoing long-standing persistent AF ablation. Patients with long-standing persistent AF (age, 68±7 years; left atrium diameter, 46±3 mm; and AF duration, 25±15 months) underwent AF ablation, LAA electric isolation, and occlusion. Outcomes were compared with a balanced (1:2 ratio) control group who had AF ablation alone. Among 22 patients who underwent ablation, LAA electric isolation was possible in 20. Intraprocedural LAA reconnection occurred in 17 of 20 (85%) patients, predominantly at anterior and superior locations. All were reisolated. LAA occlusion was successful in all 20 patients. There were no major periprocedural complications. Imaging at 45 days and 9 months confirmed satisfactory device position and excluded pericardial effusion. One of twenty (5%) patients had a gap of ≥5 mm requiring anticoagulation. Nineteen of twenty (95%) patients stopped warfarin at 3 months. Without antiarrhythmic drugs, freedom from AF at 12 months after a single procedure was significantly higher in the study group (19/20, 95%) than in the control group (25/40, 63%), P=0.036. Freedom from atrial arrhythmias was demonstrated in 12 of 20 (60%) and 18 of 20 (90%) patients after 1 and ≤2 procedures (mean, 1.3), respectively. Persistent AF ablation, LAA electric isolation, and mechanical occlusion can be performed concomitantly. This technique may improve the success of persistent AF ablation while obviating the need for chronic anticoagulation. URL: https://clinicaltrials.gov. Unique identifier: NCT02028130. © 2016 American Heart Association, Inc.

Annotated Bibliography of Armed Services Vocational Aptitude Battery (ASVAB) Validity Studies

DTIC Science & Technology

1990-02-01

research to study reading skills of applicants for military service. Understanding the nature of literacy and the relationships of literacy to aptitude...NORMS (see POPULATION, NORMS) NORMING AF68001 AF75001 AF76006 AS80002 AS84002 CV84002 CV85002 CV80001 MC86005 NV84002 NUMERICAL SKILLS (see LITERACY ...characteristic of interest. Ability, as a construct, should derive its meaning from a conceptual framework, the pattern of relationships among variables

Genetic Obesity and the Risk of Atrial Fibrillation – Causal Estimates from Mendelian Randomization

PubMed Central

Chatterjee, Neal A.; Arking, Dan E.; Ellinor, Patrick T.; Heeringa, Jan; Lin, Honghuang; Lubitz, Steven A.; Soliman, Elsayed Z.; Verweij, Niek; Alonso, Alvaro; Benjamin, Emelia J.; Gudnason, Vilmundur; Stricker, Bruno H. C.; Van Der Harst, Pim; Chasman, Daniel I.; Albert, Christine M.

2017-01-01

Background Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding, reverse causation, and bias. The primary objective of this study was to evaluate the causal association between BMI and AF using genetic predictors of BMI. Methods We identified 51 646 individuals of European ancestry without AF at baseline from seven prospective population-based cohorts initiated between 1987 and 2002 in the United States, Iceland, and the Netherlands with incident AF ascertained between 1987 and 2012. Cohort-specific mean follow-up ranged 7.4 to 19.2 years, over which period there were a total of 4178 cases of incident AF. We performed a Mendelian randomization with instrumental variable analysis to estimate a cohort-specific causal hazard ratio for the association between BMI and AF. Two genetic instruments for BMI were utilized: FTO genotype (rs1558902) and a BMI gene score comprised of 39 single nucleotide polymorphisms identified by genome-wide association studies to be associated with BMI. Cohort-specific estimates were combined by random-effects, inverse variance weighted meta-analysis. Results In age- and sex-adjusted meta-analysis, both genetic instruments were significantly associated with BMI (FTO: 0.43 [95% CI: 0.32 – 0.54] kg/m2 per A-allele, p<0.001); BMI gene score: 1.05 [95% CI: 0.90-1.20] kg/m2 per 1 unit increase, p<0.001) and incident AF (FTO – HR: 1.07 [1.02-1.11] per A-allele, p=0.004; BMI gene score – HR: 1.11 [1.05-1.18] per 1-unit increase, p<0.001). Age- and sex-adjusted instrumental variable estimates for the causal association between BMI and incident AF were HR 1.15 [1.04-1.26] per kg/m2, p=0.005 (FTO) and 1.11 [1.05-1.17] per kg/m2, p<0.001 (BMI gene score). Both of these estimates were consistent with the meta-analyzed estimate between observed BMI and AF (age- and sex-adjusted HR 1.05 [1.04-1.06] per kg/m2, p<0.001). Multivariable adjustment did not significantly change findings. Conclusions Our data are consistent with a causal relationship between BMI and incident AF. These data support the possibility that public health initiatives targeting primordial prevention of obesity may reduce the incidence of AF. PMID:27974350

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

PubMed

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

2017-11-07

Asymptomatic atrial fibrillation (AF) is increasingly common in the aging population and implicated in many ischemic strokes. Earlier identification of AF with appropriate anticoagulation may decrease stroke morbidity and mortality. We conducted a randomized controlled trial of AF screening using an AliveCor Kardia monitor attached to a WiFi-enabled iPod to obtain ECGs (iECGs) in ambulatory patients. Patients ≥65 years of age with a CHADS-VASc score ≥2 free from AF were randomized to the iECG arm or routine care (RC). iECG participants acquired iECGs twice weekly over 12 months (plus additional iECGs if symptomatic) onto a secure study server with overread by an automated AF detection algorithm and by a cardiac physiologist and/or consultant cardiologist. Time to diagnosis of AF was the primary outcome measure. The overall cost of the devices, ECG interpretation, and patient management were captured and used to generate the cost per AF diagnosis in iECG patients. Clinical events and patient attitudes/experience were also evaluated. We studied 1001 patients (500 iECG, 501 RC) who were 72.6±5.4 years of age; 534 were female. Mean CHADS-VASc score was 3.0 (heart failure, 1.4%; hypertension, 54%; diabetes mellitus, 30%; prior stroke/transient ischemic attack, 6.5%; arterial disease, 15.9%; all CHADS-VASc risk factors were evenly distributed between groups). Nineteen patients in the iECG group were diagnosed with AF over the 12-month study period versus 5 in the RC arm (hazard ratio, 3.9; 95% confidence interval=1.4-10.4; P =0.007) at a cost per AF diagnosis of $10 780 (£8255). There was a similar number of stroke/transient ischemic attack/systemic embolic events (6 versus 10, iECG versus RC; hazard ratio=0.61; 95% confidence interval=0.22-1.69; P =0.34). The majority of iECG patients were satisfied with the device, finding it easy to use without restricting activities or causing anxiety. Screening with twice-weekly single-lead iECG with remote interpretation in ambulatory patients ≥65 years of age at increased risk of stroke is significantly more likely to identify incident AF than RC over a 12-month period. This approach is also highly acceptable to this group of patients, supporting further evaluation in an appropriately powered, event-driven clinical trial. URL: https://www.isrctn.com. Unique identifier: ISRCTN10709813. © 2017 American Heart Association, Inc.

Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis.

PubMed

Yo, Chia-Hung; Lee, Si-Huei; Chang, Shy-Shin; Lee, Matthew Chien-Hung; Lee, Chien-Chang

2014-02-20

We performed a systematic review and meta-analysis of studies on high-sensitivity C-reactive protein (hs-CRP) assays to see whether these tests are predictive of atrial fibrillation (AF) recurrence after cardioversion. Systematic review and meta-analysis. PubMed, EMBASE and Cochrane databases as well as a hand search of the reference lists in the retrieved articles from inception to December 2013. This review selected observational studies in which the measurements of serum CRP were used to predict AF recurrence. An hs-CRP assay was defined as any CRP test capable of measuring serum CRP to below 0.6 mg/dL. We summarised test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. Meta-regression analysis was performed to explore the source of heterogeneity. We included nine qualifying studies comprising a total of 347 patients with AF recurrence and 335 controls. A CRP level higher than the optimal cut-off point was an independent predictor of AF recurrence after cardioversion (summary adjusted OR: 3.33; 95% CI 2.10 to 5.28). The estimated pooled sensitivity and specificity for hs-CRP was 71.0% (95% CI 63% to 78%) and 72.0% (61% to 81%), respectively. Most studies used a CRP cut-off point of 1.9 mg/L to predict long-term AF recurrence (77% sensitivity, 65% specificity), and 3 mg/L to predict short-term AF recurrence (73% sensitivity, 71% specificity). hs-CRP assays are moderately accurate in predicting AF recurrence after successful cardioversion.

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

PubMed

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

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

Women hospitalized with atrial fibrillation: gender differences, trends and outcome from a 20-year registry in a Middle Eastern country (1991-2010).

PubMed

Salam, Amar M; AlBinali, Hajar A; Al-Mulla, Abdul Wahid; Asaad, Nidal; Singh, Rajvir; Al-Qahtani, Awad; Al Suwaidi, Jassim

2013-09-30

Most of the published research on atrial fibrillation (AF) is limited to studies in the developed world and included mainly Caucasian patients. Data about women with AF among other ethnicities is very limited. The aim of this study was to compare the clinical characteristics, treatment and outcome of women to men hospitalized with AF in a middle-eastern country. Retrospective analysis of prospective registry of all patients hospitalized with AF in Qatar from 1991 through 2010 was made. Clinical characteristics, management, and outcomes of AF patients were compared according to gender. During the 20-years period; 1417 women and 2432 men were hospitalized for AF. Women were 5 years older and more likely to have diabetes mellitus, hypertension, and chronic renal impairment and were also less likely to be current smokers and to have ischemic heart disease and impaired left ventricular function when compared to men. There was no gender preference in the use of anticoagulation. The prevalence of concomitant ischemic heart disease and hypertension increased, while the prevalence of valvular heart disease and heart failure decreased among patients hospitalized with AF over the study period. In-hospital mortality and stroke rates were comparable between the two groups. Women hospitalized with atrial fibrillation were older in age and had higher prevalence of co-morbid cardiovascular risk factors compared to men whereas, mortality and stroke rates were comparable. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Histopathological Study of Left and Right Atria in Isolated Rheumatic Mitral Stenosis With and Without Atrial Fibrillation.

PubMed

Shenthar, Jayaprakash; Kalpana, Saligrama Ramegowda; Prabhu, Mukund A; Rai, Maneesh K; Nagashetty, Ravikumar Kalyani; Kamlapurkar, Giridhar

2016-09-01

Mitral stenosis (MS) has the highest incidence of atrial fibrillation (AF) in chronic rheumatic valvular disease. There are very few studies in isolated MS comparing histopathological changes in patients with sinus rhythm (SR) and AF. To analyze the histological changes associated with isolated MS and compare between changes in AF and SR. This was a prospective study in patients undergoing valve replacement surgery for symptomatic isolated MS who were divided into 2 groups, Group I AF (n = 13) and Group II SR (n = 10). Intra-operative biopsies performed from 5 different sites from both atria were analyzed for 10 histopathologic changes commonly associated with AF. On multivariate analysis, myocytolysis (odds ratio [OR]: 1.48, P = 0.05) was found to be associated with AF, whereas myocyte hypertrophy (OR: 0.21, P = 0.003), and glycogen deposition (OR: 0.43, P = 0.002) was associated with SR. Interstitial fibrosis the commonest change was uniformly distributed across both atria irrespective of the rhythm. In rheumatic MS, SR is associated with myocyte hypertrophy whereas AF is associated with myocytolysis. Endocardial inflammation is more common in left atrial appendage irrespective of rhythm. Interstitial fibrosis is seen in >90% of patients distributed in both the atria and is independent of the rhythm. Amyloid and Aschoff bodies are uncommon and the rest of the changes are uniformly distributed across both the atria. © 2016 Wiley Periodicals, Inc.

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.

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.

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.

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

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.

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.

Heart rate variability parameters in horses distinguish atrial fibrillation from sinus rhythm before and after successful electrical cardioversion.

PubMed

Broux, B; De Clercq, D; Decloedt, A; Ven, S; Vera, L; van Steenkiste, G; Mitchell, K; Schwarzwald, C; van Loon, G

2017-11-01

Atrial fibrillation (AF) is the most common pathological arrhythmia in horses. After successful treatment, recurrence is common. Heart rate monitors are easily applicable in horses and some devices offer basic heart rate variability (HRV) calculations. If HRV can be used to distinguish between AF and sinus rhythm (SR), this could become a monitoring tool for horses at risk for recurrence of AF. The purpose of this study was to assess whether in horses AF (before cardioversion) and SR (after cardioversion) can be differentiated based upon HRV parameters. Cohort study with internal controls. Six HRV parameters were determined in 20 horses, both in AF and in SR, at rest (2- and 5-min and 1- and 4-h recordings) and during exercise (walk and trot, 2-min recordings). Time-domain (standard deviation of the NN intervals, root mean squared successive differences in NN intervals and triangular index), frequency domain (low/high frequency ratio) and nonlinear parameters (standard deviation of the Poincaré plot [SD]1 and SD2) were used. Statistical analysis was done using paired Wilcoxon signed rank tests and receiver operating characteristic curves. HRV was higher during AF compared to SR. Results for the detection of AF were good (area under the receiver operating characteristic curve [AUC] 0.8-1) for most HRV parameters. Root mean squared successive differences in NN intervals and SD1 yielded the best results (AUC 0.9-1). Sensitivity and specificity were high for all parameters at all recordings, but highest during exercise. Although AUCs improved with longer recordings, short recordings were also good (AUC 0.8-1) for the detection of AF. In horses with frequent second degree atrioventricular block, HRV at rest is increased and recordings at walk or trot are recommended. Animals served as their own controls and there was no long-term follow-up to identify AF recurrence. AF (before cardioversion) and SR (after cardioversion) could be distinguished with HRV. This technique has promise as a monitoring tool in horses at risk for AF development. © 2017 EVJ Ltd.

Does Assessment for Learning Work to Promote Student Learning? The England Paradigm

ERIC Educational Resources Information Center

Vlachou, Maria A.

2015-01-01

Assessment for Learning (AfL) has influenced the assessment policy of many countries around the world because a range of research studies have shown the effectiveness of AfL on student learning. In the English context, although significant AfL developments have taken place in schools, its implementation seems not to have produced significant and…

Genetic variants related to height and risk of atrial fibrillation: the cardiovascular health study.

PubMed

Rosenberg, Michael A; Kaplan, Robert C; Siscovick, David S; Psaty, Bruce M; Heckbert, Susan R; Newton-Cheh, Christopher; Mukamal, Kenneth J

2014-07-15

Increased height is a known independent risk factor for atrial fibrillation (AF). However, whether genetic determinants of height influence risk is uncertain. In this candidate gene study, we examined the association of 209 height-associated single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of European descent from the Cardiovascular Health Study, a prospective cohort study of older adults (aged ≥ 65 years) enrolled in 1989-1990. After a median follow-up period of 13.2 years, 879 participants developed incident AF. The height-associated SNPs together explained approximately 10% of the variation in height (P = 6.0 × 10(-8)). Using an unweighted genetic height score, we found a nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95% confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that genetically predicted height was strongly associated with AF risk (per 10 cm, hazard ratio = 1.30, 95% confidence interval: 1.03, 1.64; P = 0.03). Importantly, for all models, the inclusion of actual height completely attenuated the genetic height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was independently associated with AF and may warrant future study. In conclusion, we found that genetic determinants of height appear to increase the risk of AF, primarily via height itself. This approach of examining SNPs associated with an intermediate phenotype should be considered as a method for identifying novel genetic targets. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis

PubMed Central

Yo, Chia-Hung; Lee, Si-Huei; Chang, Shy-Shin; Lee, Matthew Chien-Hung; Lee, Chien-Chang

2014-01-01

Objectives We performed a systematic review and meta-analysis of studies on high-sensitivity C-reactive protein (hs-CRP) assays to see whether these tests are predictive of atrial fibrillation (AF) recurrence after cardioversion. Design Systematic review and meta-analysis. Data sources PubMed, EMBASE and Cochrane databases as well as a hand search of the reference lists in the retrieved articles from inception to December 2013. Study eligibility criteria This review selected observational studies in which the measurements of serum CRP were used to predict AF recurrence. An hs-CRP assay was defined as any CRP test capable of measuring serum CRP to below 0.6 mg/dL. Primary and secondary outcome measures We summarised test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. Meta-regression analysis was performed to explore the source of heterogeneity. Results We included nine qualifying studies comprising a total of 347 patients with AF recurrence and 335 controls. A CRP level higher than the optimal cut-off point was an independent predictor of AF recurrence after cardioversion (summary adjusted OR: 3.33; 95% CI 2.10 to 5.28). The estimated pooled sensitivity and specificity for hs-CRP was 71.0% (95% CI 63% to 78%) and 72.0% (61% to 81%), respectively. Most studies used a CRP cut-off point of 1.9 mg/L to predict long-term AF recurrence (77% sensitivity, 65% specificity), and 3 mg/L to predict short-term AF recurrence (73% sensitivity, 71% specificity). Conclusions hs-CRP assays are moderately accurate in predicting AF recurrence after successful cardioversion. PMID:24556243

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

Management of atrial fibrillation in the post-cardiac surgery setting.

PubMed

Daoud, Emile G

2004-02-01

New onset postcardiac surgery AF is a prevalent problem associated with increased morbidity, hospital expense, and length of stay. Those agents that inhibit beta-adrenergic receptors (class II beta-blockers, sotalol, and amiodarone) have been demonstrated to be successful prophylaxis against postoperative AF. Furthermore, those therapies that do not inhibit beta-receptors are not effective prophylactic agents. Until comparative trials demonstrate a significant reduction in postoperative AF without additional adverse effects for sotalol or amiodarone compared with beta-blockers, class II beta-blockers are the preferred prophylactic therapy. If patients are deemed unable to take beta-blockers, amiodarone is likely the best alternative. Although prophylaxis against postoperative AF seems prudent, the impact of prophylactic therapy on length of stay and hospital costs has not been a primary objective of any randomized trial. Furthermore, no studies have compared prophylactic therapy for every patient versus therapy only for those patients who experience AF after heart surgery. In the absence of data from randomized clinical trials, postoperative AF should be managed in a similar fashion to clinical AF with attention to rate control, anticoagulation, and restoration of sinus rhythm.

[Comparative analysis of phenomenology of paroxysms of atrial fibrillation and panic attacks].

PubMed

San'kova, T A; Solov'eva, A D; Nedostup, A V

2004-01-01

To study phenomenology of attacks of atrial fibrillation (AF) and to compare it with phenomenology of panic attacks for elucidation of pathogenesis of atrial fibrillation and for elaboration of rational therapeutic intervention including those aimed at correction of psychovegetative abnormalities. Patients with nonrheumatic paroxysmal AF (n=105) and 100 patients with panic attacks (n=100). Clinical, cardiological and neurological examination, analysis of patients complaints during attacks of AF, and comparison them with diagnostic criteria for panic attack. It was found that clinical picture of attacks of AF comprised vegetative, emotional and functional neurological phenomena similar to those characteristic for panic attacks. This similarity as well as positive therapeutic effect of clonazepam allowed to propose a novel pathogenic mechanism of AF attacks. Severity of psychovegetative disorders during paroxysm of AF could be evaluated by calculation of psychovegetative iudex: Psychovegetative index should be used for detection of panic attack-like component in clinical picture of AF paroxysm and thus for determination of indications for inclusion of vegetotropic drugs, e. g. clonazepam, in complex preventive therapy.

The Effect of Combination of Video Feedback and Audience Feedback on Social Anxiety: Preliminary Findings.

PubMed

Chen, Junwen; Mak, Rebecca; Fujita, Satoko

2015-09-01

Although video feedback (VF) is shown to improve appraisals of social performance in socially anxious individuals, its impact on state anxiety during a social situation is mixed. The current study investigated the effect of combined video feedback and audience feedback (AF) on self-perceptions of performance and bodily sensations as well as state anxiety pertaining to a speech task. Forty-one socially anxious students were randomly allocated to combined video feedback with audience feedback (VF + AF), video feedback only (VF), audience feedback only (AF), or a control condition. Following a 3-min speech, participants in the VF + AF, VF, and AF conditions watched the videotape of their speech with cognitive preparation in the presence of three confederates who served as audience, and/or received feedback from the confederates, while the control group watched their videotaped speech without cognitive preparation. Both VF + AF and AF conditions improved distorted appraisal of performance and bodily sensations as well as state anxiety. The clinical implications of these findings are discussed. © The Author(s) 2015.

Perspectives and challenges of antioxidant therapy for atrial fibrillation.

PubMed

Gasparova, Iveta; Kubatka, Peter; Opatrilova, Radka; Caprnda, Martin; Filipova, Slavomira; Rodrigo, Luis; Malan, Leone; Mozos, Ioana; Rabajdova, Miroslava; Nosal, Vladimir; Kobyliak, Nazarii; Valentova, Vanda; Petrovic, Daniel; Adamek, Mariusz; Kruzliak, Peter

2017-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with significant morbidity and mortality. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. There is growing evidence that oxidative stress is involved in the pathogenesis of AF. Many known triggers of oxidative stress, such as age, diabetes, smoking, and inflammation, are linked with an increased risk of arrhythmia. Numerous preclinical studies and clinical trials reported the importance of antioxidant therapy in the prevention of AF, using vitamins C and E, polyunsaturated fatty acids, statins, or nitric oxide donors. The aim of our work is to give a current overview and analysis of opportunities, challenges, and benefits of antioxidant therapy in AF.

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

PubMed

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

2010-06-01

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

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.

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.

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.

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.

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.

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

The associations between atrial fibrillation and parameters of nutritional status assessment in the general hospital population - a cross-sectional analysis of medical documentation.

PubMed

Budzyński, Jacek; Anaszewicz, Marzena

2017-01-01

Atrial fibrillation (AF) and nutrition status abnormalities are two of the most significant epidemics in current health care. The aim of this study was to determine the relationship between the prevalence and outcome of AF, and the parameters of nutritional status among consecutive, real-life patients hospitalised in a university hospital. Analysis of the medical documentation of 4930 consecutive patients aged ≥ 18 years hospitalised for more than one day with diagnoses of cardiovascular disorders. Patients admitted with a diagnosis of AF (n = 512) compared to their counterparts without AF less frequently had an NRS-2002 score ≥ 3, normal range of body mass index (BMI), higher blood haemoglobin, and lower low density lipoprotein cholesterol (LDL-C) concentration. In logistic regression analysis, the risk of a hospitalisation due to AF was negatively related to BMI, NRS-2002 score, and the value of the difference between ideal and actual body mass. Urgent admission and having an NRS-2002 score ≥ 3 remained the only significant variables determining the risk of in-hospital death. Blood concentration of LDL-C and urgent admission were the only significant variables determining risk of 30-day rehospitalisation in the studied population. Inpatients with AF had a lower prevalence of normal body mass. Patients with an AF diagnosis had different risk factors for in-hospital death and 30-day rehospitalisation than their counterparts with diagnosis of cardiovascular diseases but without AF; however, the parameters of nutritional status played an important role in both patient groups. The obesity and cholesterol paradoxes were also observed.

Compromised redox homeostasis, altered nitroso-redox balance, and therapeutic possibilities in atrial fibrillation.

PubMed

Simon, Jillian N; Ziberna, Klemen; Casadei, Barbara

2016-04-01

Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso-redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Multi-scale Structural and Tensile Mechanical Response of Annulus Fibrosus to Osmotic Loading

PubMed Central

Han, Woojin M.; Nerurkar, Nandan L.; Smith, Lachlan J.; Jacobs, Nathan T.; Mauck, Robert L.; Elliott, Dawn M.

2012-01-01

This study investigates differential multi-scale structure and function relationships of the outer and inner annulus fibrosus (AF) to osmotic swelling in different buffer solutions by quantifying tensile mechanics, GAG content, water content and tissue swelling, and collagen fibril ultrastructure. In the outer AF, the tensile modulus decreased by over 70% with 0.15M PBS treatment but was unchanged with 2M PBS treatment. Moreover, the modulus loss following 0.15M PBS treatment was reversed when followed by 2M PBS treatment, potentially from increased interfibrillar and interlamellar shearing associated with fibril swelling. In contrast, the inner AF tensile modulus was unchanged by 0.15M PBS treatment and increased following 2M treatment. Transmission electron microscopy revealed that the mean collagen fibril diameters of the untreated outer and inner AF were 87.8 ± 27.9 and 71.0 ± 26.9 nm, respectively. In the outer AF, collagen fibril swelling was observed with both 0.15M and 2M PBS treatments, but inherently low GAG content remained unchanged. In the inner AF, 2M PBS treatment caused fibril swelling and GAG loss, suggesting that GAG plays a role in maintaining the structure of collagen fibrils leading to modulation of the native tissue mechanical properties. These results demonstrate important regional variations in structure and composition, and their influence on the heterogeneous mechanics of the AF. Moreover, because the composition and structure is altered as a consequence of progressive disc degeneration, quantification of these interactions is critical for study of the AF pathogenesis of degeneration and tissue engineering. PMID:22314837

Cost-of-illness studies of atrial fibrillation: methodological considerations.

PubMed

Becker, Christian

2014-10-01

Atrial fibrillation (AF) is the most common heart rhythm arrhythmia, which has considerable economic consequences. This study aims to identify the current cost-of-illness estimates of AF; a focus was put on describing the studies' methodology. A literature review was conducted. Twenty-eight cost-of-illness studies were identified. Cost-of-illness estimates exist for health insurance members, hospital and primary care populations. In addition, the cost of stroke in AF patients and the costs of post-operative AF were calculated. The methods used were heterogeneous, mostly studies calculated excess costs. The identified annual excess costs varied, even among studies from the USA (∼US$1900 to ∼US$19,000). While pointing toward considerable costs, the cost-of-illness studies' relevance could be improved by focusing on subpopulations and treatment mixes. As possible starting points for subsequent economic studies, the methodology of cost-of-illness studies should be taken into account using methods, allowing stakeholders to find suitable studies and validate estimates.

Maternal Serum and Amniotic Fluid Inhibin A Levels in Women who Subsequently Develop Severe Preeclampsia

PubMed Central

Kim, Shin-Young; Yang, Jae-Hyug; Kim, Moon-Young; Ahn, Hyun-Kyong; Shin, Joong-Sik; Choi, Jun-Seek; Park, So-Yeon; Kim, Jin-Mi; Lee, Bom-Yi; Kim, Do-Jin

2006-01-01

The purpose of this study was to evaluate whether maternal serum (MS) and amniotic fluid (AF) inhibin A levels are elevated in patients who subsequently develop severe preecalmpsia, and to investigate the correlation between MS and AF inhibin A levels in the second trimester. The study included 40 patients who subsequently developed severe preecalmpsia and 80 normal pregnant women. Inhibin A levels in MS and AF were measured with enzyme-linked immunosorbent assay (ELISA). The MS and AF inhibin A levels in patients who developed severe preeclampsia were significantly higher than those in the control group (both for p<0.001). There was a positive correlation between MS and AF inhibin A levels in patients who developed severe preeclampsia (r=0.397, p=0.011), but not in the control group (r=0.185, p=0.126). The best cutoff values of MS and AF inhibin A levels for the prediction of severe preeclampsia were 427 pg/mL and 599 pg/mL, respectively; the estimated ORs that were associated with these cut-off values were 9.95 (95% CI 3.8-25.9, p<0.001) and 6.0 (95% CI 2.3-15.8, p<0.001). An elevated level of inhibin A in MS and AF at the time of second trimester amniocentesis may be a risk factor for the subsequent development of severe preeclampsia. PMID:16778388

Sorption of sulphamethoxazole by the biochars derived from rice straw and alligator flag.

PubMed

Li, Tingqiang; Han, Xuan; Liang, Chengfeng; Shohag, M J I; Yang, Xiaoe

2015-01-01

The sorption ability of sulphamethoxazole (SMX) by biochar derived from rice straw (RS) and alligator flag (AF) at 600°C was studied to assess the ability of biochar as adsorbent to remove SMX from aqueous solution. The results indicated that sorption of SMX by biochars was well described using the Langmuir equation (R2>0.94), and the maximum sorption parameter (Q) of RS (3650 mg kg(-1)) was much higher than that of AF (1963 mg kg(-1)). Temperature had no effect on SMX sorption by biochars, while thermodynamics analysis indicated that the sorption of SMX on both biochars was a spontaneous physical process. The d 250 RS (diameter of RS sieved through 250 µm) and d 150 AF (diameter of AF sieved through 150 µm) showed excellent sorption ability for SMX. The sorption amount of RS was larger than that of AF when pH<7, whereas, the sorption amount of AF surpassed RS when pH≥7. The presence of Cu2+ and/or Cd2+ ion at low concentrations (20 mg L(-1)) significantly (P<0.05) increased the sorption of SMX on both RS and AF. Our study confirms that biochar derived from the wetland plants could be used as effective adsorbents to remove SMX from aqueous solution.

A study of monoamine oxidase activity in fetal membranes.

PubMed

Sekizawa, A; Ishikawa, H; Morimoto, T; Hirose, K; Suzuki, A; Saito, H; Yanaihara, T; Arai, Y; Oguchi, K

1996-05-01

To study the role of decidual monoamine oxidase (MAO)-A and -B activities before delivery, the relationship between MAO activity in fetal membranes and catecholamine (CA) concentration in amniotic fluid (AF) was determined. Fetal membranes and AF were obtained at the time of elective Cesarean section (CS group, n = 11) and Cesarean section due to fetal distress without labor pains (FD group, n = 5). MAO-A and -B activities were radiometrically measured using 14C-5-hydroxytriptamine for MAO-A substrate and 14C-benzylamine for MAO-B substrate. CA concentrations in AF were measured by high performance liquid chromatograph with an electro-chemical detector. Both MAO-A and -B activities in decidua obtained from CS were significantly lower than those obtained from FD. Both norepinephrine (NE) and epinephrine (EP) concentrations were significantly lower in the CS group than the FD group. A significant positive correlation between decidual MAO-A activity and NE concentration in AF was observed. No significant correlation was observed between MAO-B activity and the concentration of NE in AF. There was no correlation between EP concentrations and MAO activities. These results suggest that CA concentration in AF may be related to the activity of MAO in fetal membranes, determined by certain physiological processes during pregnancy. It has been suggested that metabolism of monoamines in fetal membranes also plays an important role in reducing monoamine influx into maternal myometrium from the AF.

CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor.

PubMed

Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Docheva, Nikolina; Dong, Zhong; Kim, Chong Jai; Kim, Yeon Mee; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S; Erez, Offer; Korzeniewski, Steven J

2017-07-01

To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM). This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay. (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm. Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.

Long-term outcomes following high intensity focused ultrasound ablation for atrial fibrillation.

PubMed

Davies, Edward J; Bazerbashi, Samer; Asopa, Sanjay; Haywood, Guy; Dalrymple-Hay, Malcolm

2014-01-01

The aim of this study is to assess the safety and efficacy of the Epicor high intensity focused ultrasound (St. Jude, Inc.®, Minneapolis, MN, USA) system using seven-day ambulatory electrocardiogram (ECG) monitoring over a two-year follow-up period. One hundred and ten patients undergoing ablation were included from a single center between January 2006 and December 2009. Rhythm was assessed using seven-day ambulatory ECG or permanent pacemaker interrogation. Seventeen patients were lost to follow-up, seven through death. Results were reported according to atrial fibrillation (AF) class preoperatively: paroxysmal, persistent, and long-standing persistent (LSP). Forty-nine percent of patients remained in sinus rhythm at greater than two years. The percentage of patients in sinus rhythm according to preoperative AF class were 81% (paroxysmal AF), 56% (persistent AF), and 18% (long-standing AF). The class of AF prior to surgery, left atrium size, and body mass index determined the long-term outcome. There were no procedure-related complications. We conclude that high intensity focused ultrasound ablation for atrial fibrillation using the Epicor system is safe and effective for surgical patients with paroxysmal AF. The persistent and LSP AF results suggest that alternative ablation strategies should be considered for these patients. © 2013 Wiley Periodicals, Inc.

Atrial fibrillation and silent stroke: links, risks, and challenges.

PubMed

Hahne, Kathrin; Mönnig, Gerold; Samol, Alexander

2016-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a projected number of 1 million affected subjects in Germany. Changes in age structure of the Western population allow for the assumption that the number of concerned people is going to be doubled, maybe tripled, by the year 2050. Large epidemiological investigations showed that AF leads to a significant increase in mortality and morbidity. Approximately one-third of all strokes are caused by AF and, due to thromboembolic cause, these strokes are often more severe than those caused by other etiologies. Silent brain infarction is defined as the presence of cerebral infarction in the absence of corresponding clinical symptomatology. Progress in imaging technology simplifies diagnostic procedures of these lesions and leads to a large amount of diagnosed lesions, but there is still no final conclusion about frequency, risk factors, and clinical relevance of these infarctions. The prevalence of silent strokes in patients with AF is higher compared to patients without AF, and several studies reported high incidence rates of silent strokes after AF ablation procedures. While treatment strategies to prevent clinically apparent strokes in patients with AF are well investigated, the role of anticoagulatory treatment for prevention of silent infarctions is unclear. This paper summarizes developments in diagnosis of silent brain infarction and its context to AF.

[Improvement of acetic acid tolerance and fermentation performance of industrial Saccharomyces cerevisiae by overexpression of flocculent gene FLO1 and FLO1c].

PubMed

Du, Zhaoli; Cheng, Yanfei; Zhu, Hui; He, Xiuping; Zhang, Borun

2015-02-01

Flocculent gene FLO1 and its truncated form FLO1c with complete deletion of repeat unit C were expressed in a non-flocculent industrial strain Saccharomyces cerevisiae CE6 to generate recombinant flocculent strains 6-AF1 and 6-AF1c respectively. Both strains of 6-AF1 and 6-AF1c displayed strong flocculation and better cell growth than the control strain CE6-V carrying the empty vector under acetic acid stress. Moreover, the flocculent strains converted glucose to ethanol at much higher rates than the control strain CE6-V under acetic acid stress. In the presence of 0.6% (V/V) acetic acid, the average ethanol production rates of 6-AF1 and 6-AF1c were 1.56 and 1.62 times of that of strain CE6-V, while the ethanol production rates of 6-AF1 and 6-AF1c were 1.21 and 1.78 times of that of strain CE6-V under 1.0% acetic acid stress. Results in this study indicate that acetic acid tolerance and fermentation performance of industrial S. cerevisiae under acetic acid stress can be improved largely by flocculation endowed by expression of flocculent genes, especially FLO1c.

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.

Assessment for Learning: Why Assessment Does Not Always Support Student Teachers' Learning

ERIC Educational Resources Information Center

Mumm, Kristi; Karm, Mari; Remmik, Marvi

2016-01-01

Numerous studies have dealt with the importance of assessment for learning (AfL) in higher education, arguing that AfL helps to promote students' learning and supports them in becoming self-directed learners. The majority of the recent literature focuses mainly on the role of individual aspects of AfL. Less attention has been paid to the…

Supplementation of OmniGen-AF alters the metabolic response to a glucose tolerance test in beef heifers

USDA-ARS?s Scientific Manuscript database

This study was designed to determine whether feeding OmniGen-AF to feedlot heifers would alter metabolic profiles in response to a glucose tolerance test. Heifer calves (n=184; 216±1 kg) were allocated into 2 treatment diets: 1) Control, fed a standard receiving ration, and 2) OmniGen-AF (OG), fed t...

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.

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

Incidence and characteristics of major bleeding among rivaroxaban users with renal disease and nonvalvular atrial fibrillation

PubMed Central

Patel, Manesh R.; Peacock, W. Frank; Tamayo, Sally; Sicignano, Nicholas; Hopf, Kathleen P.; Yuan, Zhong

2018-01-01

Objective Patients with nonvalvular atrial fibrillation (AF) and renal disease (RD) who receive anticoagulation therapy appear to be at greater risk of major bleeding (MB) than AF patients without RD. As observed in past studies, anticoagulants are frequently withheld from AF patients with RD due to concerns regarding bleeding. The objective of this study was to evaluate the incidence and pattern of MB in those with RD, as compared to those without RD, in a population of rivaroxaban users with nonvalvular AF. Methods Electronic medical records of over 10 million patients from the Department of Defense Military Health System were queried to identify rivaroxaban users with nonvalvular AF. A validated algorithm was used to identify MB-related hospitalizations. RD was defined through diagnostic codes present within 6 months prior to the bleeding date for MB cases and end of study participation for non-MB patients. Data were collected on patient characteristics, comorbidities, MB management, and outcomes. Results Overall, 44,793 rivaroxaban users with nonvalvular AF were identified. RD was present among 6,921 patients (15.5%). Patients with RD had a higher rate of MB than those without RD, 4.52 per 100 person-years versus 2.54 per 100 person-years, respectively. The fatal bleeding outcome rate (0.09 per 100 person-years) was identical between those with and without RD. Conclusion In this post-marketing study of 44,793 rivaroxaban users with nonvalvular AF, RD patients experienced a higher MB rate than those without RD. The higher rate of MB among those with RD may be due to the confounding effects of comorbidities. PMID:29618192

Blood transfusion and risk of atrial fibrillation after coronary artery bypass graft surgery

PubMed Central

Liu, Shengqun; Li, Zhanwen; Liu, Zhe; Hu, Zhenhua; Zheng, Gaifang

2018-01-01

Abstract The aim of this study was to systematically evaluate the effect of blood transfusion (BT) on postoperative atrial fibrillation (AF) in adult patients who had undergone coronary artery bypass grafting (CABG) surgery. PubMed, Embase, and Cochrane Library databases from inception to January 2017 were searched. Cohort studies were searched that evaluated the association between BT and the risk of postoperative AF in adult patients who had undergone CABG surgery. Study quality was assessed by using the Newcastle–Ottawa scale (NOS). A meta-analysis was performed with the random-effect model. Eight cohort studies involving 7401 AF cases and 31,069 participants were identified and included in our data analysis. The pooled odds ratio of postoperative AF in patients with BT was 1.45 (95% confidence interval, 1.26–1.67), with significant heterogeneity (P < .0001, I2 = 79%). Excluding one study that had an off-pump CABG did not significantly impact this result (odds ratio, 1.36; 95% confidence interval, 1.23–1.50; n = 7). To examine the stability of the primary results, we performed subgroup analyses. The association between BT and the risk of postoperative AF was similar, as determined in the stratified analyses conducted according to study design, type of surgery, and country. The findings of the present meta-analysis demonstrated a statistically significant increase in postoperative AF risk among adult patients with BT. Further prospective large-scale studies are needed to establish causality and to elucidate the underlying mechanisms. PMID:29517692

Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model.

PubMed

Di Bernardo, Julie; Maiden, Michael M; Hershenson, Marc B; Kunisaki, Shaun M

2014-06-01

Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Pregnant Sprague-Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control (AF-Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p<0.05). In contrast, lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF-Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia. Copyright © 2014 Elsevier Inc. All rights reserved.

Left atrial ejection force predicts the outcome after catheter ablation for paroxysmal atrial fibrillation.

PubMed

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

2018-02-01

Left atrium (LA) systolic dysfunction is observed in the early stages of atrial fibrillation (AF) prior to LA anatomical change. We investigated whether LA systolic dysfunction predicts recurrent AF after catheter ablation (CA) in patients with paroxysmal AF. We studied 106 patients who underwent CA for paroxysmal AF. LA systolic function was assessed with the LA emptying volume = Maximum LA volume (LAV max ) - Minimum LA volume (LAV min ), LA emptying fraction = [(LAV max - LAV min )/LAV max ] × 100, and LA ejection force calculated with Manning's method [LA ejection force = (0.5 × ρ × mitral valve area × A 2 )], where ρ is the blood density and A is the late-diastolic mitral inflow velocity. Recurrent AF was detected in 35/106 (33%) during 14.6 ± 9.1 months. Univariate analysis revealed reduced LA ejection force, decreased LA emptying fraction, larger LA diameter, and elevated brain natriuretic peptide as significant variables. On multivariate analysis, reduced LA ejection force and larger LA diameter were independently associated with recurrent AF. Moreover, patients with reduced LA ejection force and larger LA diameter had a higher risk of recurrent AF than preserved LA ejection force (log-rank P = 0.0004). Reduced LA ejection force and larger LA diameter were associated with poor outcome after CA for paroxysmal AF, and could be a new index to predict recurrent AF. © 2017 Wiley Periodicals, Inc.

Both Hypothyroidism and Hyperthyroidism Increase Atrial Fibrillation Inducibility in Rats

PubMed Central

Zhang, Youhua; Dedkov, Eduard I.; Teplitsky, Diana; Weltman, Nathan Y.; Pol, Christine J.; Rajagopalan, Viswanathan; Lee, Bianca; Gerdes, A. Martin

2014-01-01

Background Evidence indicates that cardiac hypothyroidism may contribute to heart failure (HF) progression. It is also known that HF is associated with an increased risk of atrial fibrillation (AF). While it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Methods and Results Thyroidectomized rats with serum confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (n=9), euthyroid (n=9) and hyperthyroid (n=9) groups. Rats received placebo, 3.3mg L-thyroxine (T4), or 20 mg T4 pellets (60 day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic function, while hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all p<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin 43 was not affected. Conclusions Both hypothyroidism and hyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and prevent cardiac arrhythmias and AF. PMID:24036190

Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats.

PubMed

Zhang, Youhua; Dedkov, Eduard I; Teplitsky, Diana; Weltman, Nathan Y; Pol, Christine J; Rajagopalan, Viswanathan; Lee, Bianca; Gerdes, A Martin

2013-10-01

Evidence indicates that cardiac hypothyroidism may contribute to heart failure progression. It is also known that heart failure is associated with an increased risk of atrial fibrillation (AF). Although it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Thyroidectomized rats with serum-confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (N=9), euthyroid (N=9), and hyperthyroid (N=9) groups. Rats received placebo, 3.3-mg l-thyroxine (T4), or 20-mg T4 pellets (60-day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic functions, whereas hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all P<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin 43 was not affected. Both hypothyroidism and hyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and to prevent cardiac arrhythmias and AF.

Non-aflatoxigenicity of commercial Aspergillus oryzae strains due to genetic defects compared to aflatoxigenic Aspergillus flavus.

PubMed

Tao, Lin; Chung, Soo Hyun

2014-08-01

Aspergillus oryzae is generally recognized as safe, but it is closely related to A. flavus in morphology and genetic characteristics. In this study, we tested the aflatoxigenicity and genetic analysis of nine commercial A. oryzae strains that were used in Korean soybean fermented products. Cultural and HPLC analyses showed that none of the commercial strains produced detectable amount of aflatoxins. According to the molecular analysis of 17 genes in the aflatoxin (AF) biosynthetic pathway, the commercial strains could be classified into three groups. The group I strains contained all the 17 AF biosynthetic genes tested in this study; the group II strains deleted nine AF biosynthetic genes and possessed eight genes, including aflG, aflI, aflK, aflL, aflM, aflO, aflP, and aflQ; the group III strains only had six AF biosynthetic genes, including aflG, aflI, aflK, aflO, aflP, and aflQ. With the reverse transcription polymerase chain reaction, the group I A. oryzae strains showed no expression of aflG, aflQ and/or aflM genes, which resulted in the lack of AF-producing ability. Group II and group III strains could not produce AF owing to the deletion of more than half of the AF biosynthetic genes. In addition, the sequence data of polyketide synthase A (pksA) of group I strains of A. oryzae showed that there were three point mutations (two silent mutations and one missense mutation) compared with aflatoxigenic A. flavus used as the positive control in this study.

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.

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

Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial.

PubMed

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

2013-05-14

This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban. There are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors. We compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial. Over a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups. Despite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation [ROCKET AF]; NCT00403767). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Nanocellulose reinforced gellan-gum hydrogels as potential biological substitutes for annulus fibrosus tissue regeneration.

PubMed

Pereira, Diana R; Silva-Correia, Joana; Oliveira, Joaquim M; Reis, Rui L; Pandit, Abhay; Biggs, Manus J

2018-04-01

Intervertebral disc (IVD) degeneration is associated with both structural damage and aging related degeneration. Annulus fibrosus (AF) defects such as annular tears, herniation and discectomy require novel tissue engineering strategies to functionally repair AF tissue. An ideal construct will repair the AF by providing physical and biological support, facilitating regeneration. The presented strategy herein proposes a gellan gum-based construct reinforced with cellulose nanocrystals (nCell) as a biological self-gelling AF substitute. Nanocomposite hydrogels were fabricated and characterized with respect to hydrogel swelling capacity, degradation rate in vitro and mechanical properties. Rheological evaluation on the nanocomposites demonstrated the GGMA reinforcement with nCell promoted matrix entanglement with higher scaffold stiffness observed upon ionic crosslinking. Compressive mechanical tests demonstrated compressive modulus values close to those of the human AF tissue. Furthermore, cell culture studies with encapsulated bovine AF cells indicated that nanocomposite constructs promoted cell viability and a physiologically relevant cell morphology for up to fourteen days in vitro. Copyright © 2017 Elsevier Inc. All rights reserved.

Atrial fibrillation in the elderly: the potential contribution of reactive oxygen species

PubMed Central

Schillinger, Kurt J.; Patel, Vickas V.

2012-01-01

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia, and is a significant source of healthcare expenditures throughout the world. It is an arrhythmia with a very clearly defined predisposition for individuals of advanced age, and this fact has led to intense study of the mechanistic links between aging and AF. By promoting oxidative damage to multiple subcellular and cellular structures, reactive oxygen species (ROS) have been shown to induce the intra- and extra-cellular changes necessary to promote the pathogenesis of AF. In addition, the generation and accumulation of ROS have been intimately linked to the cellular processes which underlie aging. This review begins with an overview of AF pathophysiology, and introduces the critical structures which, when damaged, predispose an otherwise healthy atrium to AF. The available evidence that ROS can lead to damage of these critical structures is then reviewed. Finally, the evidence linking the process of aging to the pathogenesis of AF is discussed. PMID:23341843

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.

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.

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.

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

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

PubMed

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

2004-09-01

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

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

PubMed

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

2014-05-01

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

Left atrial pressure pattern without a-wave in sinus rhythm after cardioversion affects the outcomes after catheter ablation for atrial fibrillation.

PubMed

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

2018-04-24

The a-wave in left atrial pressure (LAP) is often not observed after cardioversion (CV). We hypothesized that repeated atrial fibrillation (AF) occurs in patients who do not show a-wave pattern after CV. We investigated the impact of "LAP pattern without a-wave" on the outcome after catheter ablation (CA) for AF. We studied 100 patients (64 males, age 66 ± 8 years, 42 with non-paroxysmal AF) who underwent CA for AF. Sustained- or induced-AF were terminated with internal CV, and LAP was measured during sinus rhythm (SR) after CV. LAP pattern without a-wave was defined as absence of a-wave (the "a-wave" was defined as a protruding part by 0.2 mmHg or more from the baseline) in LAP wave form. AF was terminated with CV in all patients. Recurrent AF was detected in 35/100 (35%) during the follow-up period (13.1 ± 7.8 month). Univariate analysis revealed higher prevalence of LAP pattern without a-wave (71 vs. 17%, P < 0.0001), larger left atrial volume, elevated E wave, and decreased deceleration time as significant variables. On multivariate analysis, LAP pattern without a-wave was only independently associated with recurrent AF (P = 0.0014, OR 9.865, 95% CI 2.327-54.861). Moreover, patients with LAP pattern without a-wave had a higher risk of recurrent AF than patients with a-wave (25/36 patients, 69 vs. 10/64 patients, 16%, log-rank P < 0.0001). Left atrial pressure pattern without a-wave in sinus rhythm after cardioversion could predict recurrence after catheter ablation for AF.

Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF.

PubMed

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

2016-08-01

The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29-1.66], diabetes [1.22, (1.11-1.34)], prior MI [1.27, (1.13-1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04-1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

The fabrication and characterization of a multi-laminate, angle-ply collagen patch for annulus fibrosus repair.

PubMed

McGuire, Rachel; Borem, Ryan; Mercuri, Jeremy

2017-12-01

One major limitation of intervertebral disc (IVD) repair is that no ideal biomaterial has been developed that effectively mimics the angle-ply collagen architecture and mechanical properties of the native annulus fibrosus (AF). Furthermore, it would be beneficial to devise a simple, scalable process by which to manufacture a biomimetic biomaterial that could function as a mechanical repair patch to be secured over a large defect in the outer AF that will support AF tissue regeneration. Such a biomaterial would: (1) enable the employment of early-stage interventional strategies to treat IVD degeneration (i.e. nucleus pulposus arthroplasty); (2) prevent IVD re-herniation in patients with large AF defects; and (3) serve as a platform to develop full-thickness AF and whole IVD tissue engineering strategies. Due to the innate collagen fibre alignment and mechanical strength of pericardium, a procedure was developed to assemble multi-laminate angle-ply AF patches derived from decellularized pericardial tissue. Patches were subsequently assessed histologically to confirm angle-ply microarchitecture, and mechanically assessed for biaxial burst strength and tensile properties. Additionally, patch cytocompatibility was evaluated following seeding with bovine AF cells. This study demonstrated the effective removal of porcine cell remnants from the pericardium, and the ability to reliably produce multi-laminate patches with angle-ply architecture using a simple assembly technique. Resultant patches demonstrated their inherent ability to resist biaxial burst pressures reminiscent of intradiscal pressures commonly borne by the AF, and exhibited tensile strength and modulus values reported for native human AF. Furthermore, the biomaterial supported AF cell viability, infiltration and proliferation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Silk-based multilayered angle-ply annulus fibrosus construct to recapitulate form and function of the intervertebral disc.

PubMed

Bhunia, Bibhas K; Kaplan, David L; Mandal, Biman B

2018-01-16

Recapitulation of the form and function of complex tissue organization using appropriate biomaterials impacts success in tissue engineering endeavors. The annulus fibrosus (AF) represents a complex, multilamellar, hierarchical structure consisting of collagen, proteoglycans, and elastic fibers. To mimic the intricacy of AF anatomy, a silk protein-based multilayered, disc-like angle-ply construct was fabricated, consisting of concentric layers of lamellar sheets. Scanning electron microscopy and fluorescence image analysis revealed cross-aligned and lamellar characteristics of the construct, mimicking the native hierarchical architecture of the AF. Induction of secondary structure in the silk constructs was confirmed by infrared spectroscopy and X-ray diffraction. The constructs showed a compressive modulus of 499.18 ± 86.45 kPa. Constructs seeded with porcine AF cells and human mesenchymal stem cells (hMSCs) showed ∼2.2-fold and ∼1.7-fold increases in proliferation on day 14, respectively, compared with initial seeding. Biochemical analysis, histology, and immunohistochemistry results showed the deposition of AF-specific extracellular matrix (sulfated glycosaminoglycan and collagen type I), indicating a favorable environment for both cell types, which was further validated by the expression of AF tissue-specific genes. The constructs seeded with porcine AF cells showed ∼11-, ∼5.1-, and ∼6.7-fold increases in col I α 1 , sox 9, and aggrecan genes, respectively. The differentiation of hMSCs to AF-like tissue was evident from the enhanced expression of the AF-specific genes. Overall, the constructs supported cell proliferation, differentiation, and ECM deposition resulting in AF-like tissue features based on ECM deposition and morphology, indicating potential for future studies related to intervertebral disc replacement therapy.

ACUTE TERMINATION OF HUMAN ATRIAL FIBRILLATION BY IDENTIFICATION AND CATHETER ABLATION OF LOCALIZED ROTORS AND SOURCES

PubMed Central

Shivkumar, Kalyanam; Ellenbogen, Kenneth A.; Hummel, John D.; Miller, John M.; Steinberg, Jonathan S.

2012-01-01

Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. METHODS We prospectively enrolled the first (n=14, 11 males) consecutive patients undergoing FIRM guided ablation for persistent (n=11) and paroxysmal AF at 5 centers. A 64 pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10 % cycle length prolongation). Conventional ablation was performed only after FIRM guided ablation. RESULTS 12/14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9±0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n=8 (4.9±3.9 min at the primary source), and organization in n=4. Total FIRM time for all patients was 12.3±8.6 min. CONCLUSIONS FIRM guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. PMID:23130890

A comparison of QuantStudio™ 3D Digital PCR and ARMS-PCR for measuring plasma EGFR T790M mutations of NSCLC patients.

PubMed

Feng, Qin; Gai, Fei; Sang, Yaxiong; Zhang, Jie; Wang, Ping; Wang, Yue; Liu, Bing; Lin, Dongmei; Yu, Yang; Fang, Jian

2018-01-01

The AURA3 clinical trial has shown that advanced non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations in circulating tumor DNA (ctDNA) could benefit from osimertinib. The aim of this study was to assess the usefulness of QuantStudio™ 3D Digital PCR System platform for the detection of plasma EGFR T790M mutations in NSCLC patients, and compare the performances of 3D Digital PCR and ARMS-PCR. A total of 119 Chinese patients were enrolled in this study. Mutant allele frequency of plasma EGFR T790M was detected by 3D Digital PCR, then 25 selected samples were verified by ARMS-PCR and four of them were verified by next generation sequencing (NGS). In total, 52.94% (69/119) had EGFR T790M mutations detected by 3D Digital PCR. In 69 positive samples, the median mutant allele frequency (AF) was 1.09% and three cases presented low concentration (AF <0.1%). Limited by the amount of plasma DNA, 17 samples (AF <2.5%) and eight samples (T790M-) were selected for verification by ARMS-PCR. Four of those samples were verified by NGS as a third verification method. Among the selected 17 positive cases, ten samples presented mutant allele frequency <0.5%, and seven samples presented intermediate mutant allele frequency (0.5% AF 2.5%). However, only three samples (3/17) were identified as positive by ARMS-PCR, namely, P6 (AF =1.09%), P7 (AF =2.09%), and P8 (AF =2.21%). It is worth mentioning that sample P9 (AF =2.05%, analyzed by 3D Digital PCR) was identified as T790M- by ARMS-PCR. Four samples were identified as T790M+ by both NGS and 3D Digital PCR, and typically three samples (3/4) presented at a low ratio (AF <0.5%). Our study demonstrated that 3D Digital PCR is a novel method with high sensitivity and specificity to detect EGFR T790M mutation in plasma.

A comparison of QuantStudio™ 3D Digital PCR and ARMS-PCR for measuring plasma EGFR T790M mutations of NSCLC patients

PubMed Central

Sang, Yaxiong; Zhang, Jie; Wang, Ping; Wang, Yue; Liu, Bing; Lin, Dongmei; Yu, Yang; Fang, Jian

2018-01-01

Background The AURA3 clinical trial has shown that advanced non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations in circulating tumor DNA (ctDNA) could benefit from osimertinib. Purpose The aim of this study was to assess the usefulness of QuantStudio™ 3D Digital PCR System platform for the detection of plasma EGFR T790M mutations in NSCLC patients, and compare the performances of 3D Digital PCR and ARMS-PCR. Patients and methods A total of 119 Chinese patients were enrolled in this study. Mutant allele frequency of plasma EGFR T790M was detected by 3D Digital PCR, then 25 selected samples were verified by ARMS-PCR and four of them were verified by next generation sequencing (NGS). Results In total, 52.94% (69/119) had EGFR T790M mutations detected by 3D Digital PCR. In 69 positive samples, the median mutant allele frequency (AF) was 1.09% and three cases presented low concentration (AF <0.1%). Limited by the amount of plasma DNA, 17 samples (AF <2.5%) and eight samples (T790M-) were selected for verification by ARMS-PCR. Four of those samples were verified by NGS as a third verification method. Among the selected 17 positive cases, ten samples presented mutant allele frequency <0.5%, and seven samples presented intermediate mutant allele frequency (0.5% AF 2.5%). However, only three samples (3/17) were identified as positive by ARMS-PCR, namely, P6 (AF =1.09%), P7 (AF =2.09%), and P8 (AF =2.21%). It is worth mentioning that sample P9 (AF =2.05%, analyzed by 3D Digital PCR) was identified as T790M- by ARMS-PCR. Four samples were identified as T790M+ by both NGS and 3D Digital PCR, and typically three samples (3/4) presented at a low ratio (AF <0.5%). Conclusion Our study demonstrated that 3D Digital PCR is a novel method with high sensitivity and specificity to detect EGFR T790M mutation in plasma. PMID:29403309

Usefulness of quantitative polymerase chain reaction in amniotic fluid as early prognostic marker of fetal infection with Toxoplasma gondii.

PubMed

Romand, Stéphane; Chosson, Muriel; Franck, Jacqueline; Wallon, Martine; Kieffer, François; Kaiser, Karine; Dumon, Henri; Peyron, François; Thulliez, Philippe; Picot, Stéphane

2004-03-01

Our purpose was to evaluate Toxoplasma gondii concentration in amniotic fluid (AF) samples as a prognostic marker of congenital toxoplasmosis. A retrospective study was carried out in 88 consecutive AF samples from 86 pregnant women, which were found positive by prospective polymerase chain reaction (PCR) testing. Parasite AF concentrations were estimated by real-time quantitative PCR and analyzed in relation to the clinical outcome of infected fetuses during pregnancy and at birth, taking into account the gestational age at maternal infection. A significant negative linear regression was observed between gestational age at maternal infection and T gondii DNA loads in AF. After adjusting for time at maternal seroconversion by multivariate analysis, higher parasite concentrations were significantly associated with a severe outcome of congenital infection (odds ratio [OR]=15.38/log (parasites/mL AF) [95% CI=2.45-97.7]). PCR quantification of T gondii in AF can be highly contributive for early prognosis of congenital toxoplasmosis. Maternal infections acquired before 20 weeks with a parasite load greater than 100/mL of AF have the highest risk of severe fetal outcome.

Efficacy and safety of dronedarone: a review of randomized trials.

PubMed

Christiansen, Christine Benn; Torp-Pedersen, Christian; Køber, Lars

2010-01-01

Dronedarone is developed for treatment of atrial fibrillation (AF) or flutter (AFL). It is a noniodinized amiodarone analogue and believed to be without the adverse effects of amiodarone. However, long-term adverse effects are not yet well investigated. This is a review of seven studies on dronedarone. DAFNE established an effective dose to be 400 mg b.i.d. ADONIS and EURIDIS showed significant prevention of AF/AFL recurrence hazard ratio (HR 0.78 and 0.73) compared to placebo. In ATHENA, cardiovascular death/hospitalization was significantly reduced (HR 0.76) in patients with AF and additional risk factors. ANDROMEDA was stopped because dronedarone increased early mortality (HR 2.13) in advanced heart failure (HF). ERATO found that dronedarone significantly reduced heart rate compared to placebo in patients with AF. DIONYSOS showed that amiodarone was superior to dronedarone to maintain sinus rhythm in patients with AF/AFL. Dronedarone is superior to placebo but less efficient than amiodarone in maintaining sinus rhythm in patients with a history of AF. In patients with AF and risk factors dronedarone reduces cardiovascular mortality and morbidity, but in patients with severe HF dronedarone significantly increases mortality.

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

PubMed

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

2016-05-05

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

Dietary factors and incident atrial fibrillation: the Framingham Heart Study123

PubMed Central

Shen, Jian; Johnson, Victor M; Sullivan, Lisa M; Jacques, Paul F; Magnani, Jared W; Lubitz, Steven A; Pandey, Shivda; Levy, Daniel; Vasan, Ramachandran S; Quatromoni, Paula A; Junyent, Mireia; Ordovas, Jose M; Benjamin, Emelia J

2011-01-01

Background: There have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF). Objective: We evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study. Design: Participants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression. Results: A total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n−3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of <1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001). Conclusions: Consumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population. PMID:21106919

Usefulness of HATCH score in the prediction of new-onset atrial fibrillation for Asians.

PubMed

Suenari, Kazuyoshi; Chao, Tze-Fan; Liu, Chia-Jen; Kihara, Yasuki; Chen, Tzeng-Ji; Chen, Shih-Ann

2017-01-01

The HATCH score (hypertension <1 point>, age >75 years <1 point>, stroke or transient ischemic attack <2 points>, chronic obstructive pulmonary disease <1 point>, and heart failure <2 points>) was reported to be useful for predicting the progression of atrial fibrillation (AF) from paroxysmal to persistent or permanent AF for patients who participated in the Euro Heart Survey. The goal of the current study was to investigate whether the HATCH score was a useful scheme in predicting new-onset AF. Furthermore, we aimed to use the HATCH scoring system to estimate the individual risk in developing AF for patients with different comorbidities. We used the "Taiwan National Health Insurance Research Database." From January 1, 2000, to December 31, 2001, a total of 670,804 patients older than 20 years old and who had no history of cardiac arrhythmias were enrolled. According to the calculation rule of the HATCH score, 599,780 (score 0), 46,661 (score 1), 12,892 (score 2), 7456 (score 3), 2944 (score 4), 802 (score 5), 202 (score 6), and 67 (score 7) patients were studied and followed for the new onset of AF. During a follow-up of 9.0 ± 2.2 years, there were 9174 (1.4%) patients experiencing new-onset AF. The incidence of AF was 1.5 per 1000 patient-years. The incidence increased from 0.8 per 1000 patient-years for patients with a HATCH score of 0 to 57.3 per 1000 patient-years for those with a HATCH score of 7. After an adjustment for the gender and comorbidities, the hazard ratio (95% confidence interval) of each increment of the HATCH score in predicting AF was 2.059 (2.027-2.093; P < 0.001). The HATCH score was useful in risk estimation and stratification of new-onset AF.

TEK and biodiversity management in agroforestry systems of different socio-ecological contexts of the Tehuacán Valley.

PubMed

Vallejo-Ramos, Mariana; Moreno-Calles, Ana I; Casas, Alejandro

2016-07-22

Transformation of natural ecosystems into intensive agriculture is a main factor causing biodiversity loss worldwide. Agroforestry systems (AFS) may maintain biodiversity, ecosystem benefits and human wellbeing, they have therefore high potential for concealing production and conservation. However, promotion of intensive agriculture and disparagement of TEK endanger their permanence. A high diversity of AFS still exist in the world and their potentialities vary with the socio-ecological contexts. We analysed AFS in tropical, temperate, and arid environments, of the Tehuacan Valley, Mexico, to investigate how their capacity varies to conserve biodiversity and role of TEK influencing differences in those contexts. We hypothesized that biodiversity in AFS is related to that of forests types associated and the vigour of TEK and management. We conducted studies in a matrix of environments and human cultures in the Tehuacán Valley. In addition, we reviewed, systematized and compared information from other regions of Mexico and the world with comparable socio-ecological contexts in order to explore possible general patterns. Our study found from 26 % to nearly 90 % of wild plants species richness conserved in AFS, the decreasing proportion mainly associated to pressures for intensifying agricultural production and abandoning traditional techniques. Native species richness preserved in AFS is influenced by richness existing in the associated forests, but the main driver is how people preserve benefits of components and functions of ecosystems. Elements of modern agricultural production may coexist with traditional management patterns, but imposition of modern models may break possible balances. TEK influences decisions on what and how modern techniques may be advantageous for preserving biodiversity, ecosystem integrity in AFS and people's wellbeing. TEK, agroecology and other sciences may interact for maintaining and improving traditional AFS to increase biodiversity and ecosystem integrity while improving quality of life of people managing the AFS.

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

PubMed

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

2015-01-01

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

Inappropriate combination of warfarin and aspirin

PubMed Central

Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

2016-01-01

Objective: A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). Methods: This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Results: Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). Conclusion: The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV. (Anatol J Cardiol 2016; 16: 189-96) PMID:26467380

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: I. Reduced flow velocity in the left atrial appendage (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study).

PubMed

Goldman, M E; Pearce, L A; Hart, R G; Zabalgoitia, M; Asinger, R W; Safford, R; Halperin, J L

1999-12-01

Stroke associated with atrial fibrillation (AF) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage (LAA). Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography (TEE) in patients with AF have not been defined. To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events, we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation (SPAF-III) study. Patient features, TEE findings, and subsequent cardioembolic events were correlated with velocity by multivariate analysis. Patients in AF during TEE displayed lower peak antegrade (emptying) flow velocity (Anu(p)) than those with intermittent AF in sinus rhythm during TEE (33 cm/s vs 61 cm/s, respectively, P <.0001). Anu(p) < 20 cm/s was associated with dense spontaneous echocardiographic contrast (P <.001), appendage thrombus (P <.01), and subsequent cardioembolic events (P <.01). Independent predictors of Anu(p) < 20 cm/s included age (P =.009), systolic blood pressure (P <.001), sustained AF (P =.01), ischemic heart disease (P =.01), and left atrial area (P =.04). Multivariate analysis found both Anu(p) <20 cm/s (relative risk 2.6, P =.02) and clinical risk factors (relative risk 3.3, P =.002) independently associated with LAA thrombus. LAA Anu(p) is reduced in AF and associated with spontaneous echocardiographic contrast, appendage thrombus, and cardioembolic stroke. Systolic hypertension and aortic atherosclerosis, independent clinical predictors of stroke in patients with AF, also correlated with LAA Anu(p). Our results support the role of reduced LAA Anu(p) in the generation of stasis, thrombus formation, and embolism in patients with AF, although other mechanisms also contribute to stroke.

Addressing the management of atrial fibrillation - a systematic review of the role of dronedarone.

PubMed

Podda, Gian Marco; Casazza, Giovanni; Casella, Francesco; Dipaola, Franca; Scannella, Emanuela; Tagliabue, Ludovica

2012-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. It occurs in 1%-2% of the general population and its prevalence increases with age. Dronedarone, a noniodinated benzofuran similar to amiodarone, was developed as an antiarrhythmic agent for patients with atrial fibrillation. The aim of our systematic review was to critically evaluate randomized controlled trials that compared treatment with dronedarone versus placebo or amiodarone in patients with atrial fibrillation. Electronic databases (MEDLINE, Embase, and Central) were searched up to November 2011 with no language restrictions. We included randomized controlled trials in which dronedarone was compared to placebo or other drugs in patients with AF. Internal and external validity was assessed. We identified seven papers corresponding to eight randomized controlled trials. The DAFNE, EURIDIS/ADONIS, and ATHENA trials demonstrated a reduction of AF recurrence with dronedarone as compared to placebo in patients with nonpermanent AF. The DIONYSOS study showed that dronedarone is less effective for the prevention of recurrent AF but improved tolerability as compared to amiodarone. Considering patients with permanent AF, the ERATO trial showed that dronedarone had rate-control effects while the PALLAS study was stopped early since stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes were significantly more frequent in subjects treated with dronedarone as compared to placebo. The ANDROMEDA trial included patients with recent hospitalization for heart failure and was terminated early because of excess of deaths in the dronedarone group. Like most antiarrhythmic drugs, dronedarone reduces the recurrence of AF in patients with paroxysmal or persistent AF as compared to placebo. However, relapse rates in the first year of therapy are high. Moreover, dronedarone showed to be less effective than amiodarone. Finally, dronedarone should be avoided in patients with permanent AF and a high risk for cardiovascular events or severe congestive heart failure.

Pulmonary vein activity does not predict the outcome of catheter ablation for persistent atrial fibrillation: A long-term multicenter prospective study.

PubMed

Prabhu, Sandeep; Kalla, Manish; Peck, Kah Y; Voskoboinik, Aleksandr; McLellan, Alex J A; Pathik, Bupesh; Nalliah, Chrishan J; Wong, Geoff R; Sugumar, Hariharan; Azzopardi, Sonia M; Lee, Geoffrey; Ling, Liang-Han; Kalman, Jonathan M; Kistler, Peter M

2018-03-02

Pulmonary vein (PV) isolation (PVI) remains the cornerstone of catheter ablation (CA) in persistent atrial fibrillation (AF) (PeAF), although less successful than for paroxysmal AF. Whether rapid or fibrillatory (PV AF) PV firing may identify patients with PeAF more likely to benefit from a PV-based ablation approach is unclear. The purpose of this study was to determine the relationship between the PV cycle length (PVCL) and the PV AF outcome after CA. Before ablation, the multipolar catheter was placed in each PV and the left atrial appendage (LAA) for 100 consecutive cycles. The presence of PV AF, the average PVCL of all 4 veins (PV 4VAverage ), the fastest vein average (PV FVAverage ), the fastest cycle length (PV Fast ) both individually and relative to the average LAA cycle length were calculated. The ablation strategy included PVI and posterior wall isolation with a minimum of 12 months follow-up. A total of 123 patients underwent CA (age 62 ± 9.1 years; CHA 2 DS 2 -VASC score 1.6 ± 1.1; left ventricular ejection fraction 48% ± 13%; left atrial area 31 ± 8.7 cm 2 ; AF duration 16 ± 17 months). PVI was achieved in 100% of patients. Multiprocedure success (MPS; freedom from AF/atrial tachycardia episodes lasting >30 seconds) was achieved in 76% of patients at 24 ± 8.1 months of follow-up after 1.2 ± 0.4 procedures. PV activity was not associated with MPS either absolutely (PV 4VAverage [MPS no vs yes: 178 ± 27 ms vs 177 ± 24 ms; P = .92], PV FVAverage [P = .69], or PV Fast [P = .82]) or as a ratio relative to the LAA cycle length (PV 4VAverage /LAA 1.05 ± 0.11 vs 1.06 ± 0.21; P = .87). The presence of PV AF (31% vs 47%; P = .13) did not predict MPS. The rapidity of PV firing or presence of fibrillation within the PV was not predictive of outcome of CA for PeAF. PV activity does not identify patients most likely to benefit from a PV-based ablation strategy. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-02-01

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

[Plasma cardiac natriuretic peptide as a biological marker of recurrence of atrial fibrillation in elderly people].

PubMed

Mabuchi, N; Tsutamoto, T; Maeda, K; Masahiko, K

2000-07-01

We designed this study to evaluate the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and recurrence of atrial fibrillation (AF) after direct current cardioversion (DC) and the differences with aging. Fifty patients with mild congestive heart failure (CHF) undergoing elective DC of AF were included in this study (New York Heart Association (NYHA) functional class II: n = 42, III = 8). Patients who failed to show restoration of sinus rhythm or those with mitral valve stenosis were excluded. Before successful DC, we measured plasma levels of ANP and BNP and evaluated left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (EF) by echocardiography. Twenty-one patients had recurrence of AF within 2 months after DC (average 9.05 days). We followed up the other 29 patients for 580.5 days. By Cox stepwise multivariate analysis, history of AF (p = 0.007), low plasma levels of ANP (p = 0.003), and high plasma levels of BNP (p = 0.0003) were found to be independent predictors of recurrent AF. High plasma BNP levels indicating ventricular dysfunction and low plasma ANP levels may be due to atrial histological change such as fibrosis. In these patients, plasma ratios of ANP and BNP (ANP/BNP) less than 0.43 were predictive factors for AF recurrence (sensitivity 70%, specificity 62%), especially in patients who were older than 70 years (sensitivity 100%, specificity 80%). Relatively low plasma ANP level compared to BNP is an independent risk factor of AF recurrence in patients with CHF, especially in elderly patients, suggesting that plasma cardiac natriuretic peptides are important biochemical markers of AF recurrence in elderly patients with CHF.

Dilemma of Timing of Administration of Non-Steroidal Anti-inflammatory Agents in Relation to Food in the Prevention of Drug Induced Gastritis: Debusting the Myth.

PubMed

Udaykumar, Padmaja; Udaykumar, K; Scandashree, K; Anurag, K

2016-01-01

We aimed to identify the signals that indicate the possible benefits of administering Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) at the initiation of meal, compared to immediately after food. This was a randomized, controlled, pilot study in 160 patients who received only NSAIDs for various pain conditions. Patients were randomized to Group I (control group) -NSAID After Food (AF), Group II-NSAID Before Food (BF), Group III-NSAID BF for 2 days and then crossed over to AF for next two days (CO-1) and Group IV-NSAID AF for 2 days and then crossed over to BF for next two days (C0-2 group). Group III & Group IV were given a washout period of 48 hours after the initial two days of treatment. All were followed up for the next 2 drug free days. Patients were observed for the development of gastritis (epigastric distress, epigastric pain, nausea, fullness of stomach, repeated reflux) throughout the study. Symptoms of gastritis were seen in 6.45% (2/31) and 36.11% (13/36) patients in group I and II, respectively. There was no statistically significant difference in the development of gastritis in AF group. However, statistically significant difference (P<0.05) was found between BF group and AF intake of NSAIDs [CO-1 (AF), CO-2 (A.F), AF (control group)] in terms of development of gastritis. Administering NSAIDs at the initiation of meal is better tolerated as indicated by the lower incidence of gastritis. If proved in larger population, routine concurrent administration of medication for prevention of gastritis can be avoided.

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

PubMed

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

2007-09-01

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

Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation.

PubMed

Poulet, Claire; Künzel, Stephan; Büttner, Edgar; Lindner, Diana; Westermann, Dirk; Ravens, Ursula

2016-02-01

The contribution of human atrial fibroblasts to cardiac physiology and pathophysiology is poorly understood. Fibroblasts may contribute to arrhythmogenesis through fibrosis, or by directly altering electrical activity in cardiomyocytes. The objective of our study was to uncover phenotypic differences between cells from patients in sinus rhythm (SR) and chronic atrial fibrillation (AF), with special emphasis on electrophysiological properties. We isolated fibroblasts from human right atrial tissue for patch-clamp experiments, proliferation, migration, and differentiation assays, and gene expression profiling. In culture, proliferation and migration of AF fibroblasts were strongly impaired but differentiation into myofibroblasts was increased. This was associated with a higher number of AF fibroblasts expressing functional Nav1.5 channels. Strikingly Na(+) currents were considerably larger in AF cells. Blocking Na(+) channels in culture with tetrodotoxin did not affect proliferation, migration, or differentiation in neither SR nor AF cells. While freshly isolated fibroblasts showed mostly weak rectifier currents, fibroblasts in culture developed outward rectifier K(+) currents of similar amplitude between the SR and AF groups. Adding the K(+) channel blockers tetraethylammonium and 4-aminopyridin in culture reduced current amplitude and inhibited proliferation in the SR group only. Analysis of gene expression revealed significant differences between SR and AF in genes encoding for ion channels, collagen, growth factors, connexins, and cadherins. In conclusion, this study shows that under AF conditions atrial fibroblasts undergo phenotypic changes that are revealed in culture. Future experiments should be performed in situ to understand the nature of those changes and whether they affect cardiac electrical activity. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Long‐term Outcomes of Catheter Ablation of Atrial Fibrillation: A Systematic Review and Meta‐analysis

PubMed Central

Ganesan, Anand N.; Shipp, Nicholas J.; Brooks, Anthony G.; Kuklik, Pawel; Lau, Dennis H.; Lim, Han S.; Sullivan, Thomas; Roberts‐Thomson, Kurt C.; Sanders, Prashanthan

2013-01-01

Background In the past decade, catheter ablation has become an established therapy for symptomatic atrial fibrillation (AF). Until very recently, few data have been available to guide the clinical community on the outcomes of AF ablation at ≥3 years of follow‐up. We aimed to systematically review the medical literature to evaluate the long‐term outcomes of AF ablation. Methods and Results A structured electronic database search (PubMed, Embase, Web of Science, Cochrane) of the scientific literature was performed for studies describing outcomes at ≥3 years after AF ablation, with a mean follow‐up of ≥24 months after the index procedure. The following data were extracted: (1) single‐procedure success, (2) multiple‐procedure success, and (3) requirement for repeat procedures. Data were extracted from 19 studies, including 6167 patients undergoing AF ablation. Single‐procedure freedom from atrial arrhythmia at long‐term follow‐up was 53.1% (95% CI 46.2% to 60.0%) overall, 54.1% (95% CI 44.4% to 63.4%) in paroxysmal AF, and 41.8% (95% CI 25.2% to 60.5%) in nonparoxysmal AF. Substantial heterogeneity (I2>50%) was noted for single‐procedure outcomes. With multiple procedures, the long‐term success rate was 79.8% (95% CI 75.0% to 83.8%) overall, with significant heterogeneity (I2>50%).The average number of procedures per patient was 1.51 (95% CI 1.36 to 1.67). Conclusions Catheter ablation is an effective and durable long‐term therapeutic strategy for some AF patients. Although significant heterogeneity is seen with single procedures, long‐term freedom from atrial arrhythmia can be achieved in some patients, but multiple procedures may be required. PMID:23537812

Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

PubMed

Dewland, Thomas A; Soliman, Elsayed Z; Yamal, Jose-Miguel; Davis, Barry R; Alonso, Alvaro; Albert, Christine M; Simpson, Lara M; Haywood, L Julian; Marcus, Gregory M

2017-12-01

Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P =0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P =0.16) was not associated with a significant reduction in incident AF/AFL. Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542. © 2017 American Heart Association, Inc.

Amniotic fluid digestive enzyme analysis is useful for identifying CFTR gene mutations of unclear significance.

PubMed

Oca, Florine; Dreux, Sophie; Gérard, Bénédicte; Simon-Bouy, Brigitte; de Becdelièvre, Alix; Ferec, Claude; Girodon, Emmanuelle; Muller, Françoise

2009-12-01

The large number of CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] mutations and the existence of variants of unclear significance complicate the prenatal diagnosis of cystic fibrosis (CF). The aim of this study was to determine whether the pattern of amniotic fluid digestive enzymes (AF-DEs) could be correlated with the severity of CFTR mutations. The AF-DE pattern (gamma-glutamyltranspeptidase, aminopeptidase M, and the intestinal isoform of alkaline phosphatase) was retrospectively analyzed in 43 AF samples. All fetuses presented 2 CFTR mutations, which were classified according to the severity of the disease: CF/CF (n = 38); CF/CFTR-related disorders (n = 1); and CF/unknown variant (n = 4). The relationships between clinical CF status, CFTR mutations, and AF-DE pattern were studied. Of 38 severely affected CF fetuses, an "obstructive" AF-DE pattern was observed in 15 of 15 samples collected before 22 weeks, irrespective of the CFTR mutation (diagnostic sensitivity, 100%; diagnostic specificity, 99.8%). In the 23 fetuses evaluated after 22 weeks, the AF-DE pattern was abnormal in 7 cases and noncontributive in 16 (diagnostic sensitivity, 30.4%; diagnostic specificity, 99.8%). Of the 5 questionable cases (F508del/N1224K, F508del/L73F, 3849+10kbC>T/G1127E, F508del/S1235R, F508del/G622D), all were CF symptom free at 2-4 years of follow-up. The AF-DE pattern (<22 weeks) was typical in 3 cases but abnormal in the last 2 cases. AF-DE analysis is of value for prenatal CF diagnosis in classic forms of CF and could be helpful in nonclassic CF.

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation.

PubMed

Glasscock, Edward; Voigt, Niels; McCauley, Mark D; Sun, Qiang; Li, Na; Chiang, David Y; Zhou, Xiao-Bo; Molina, Cristina E; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G; Noebels, Jeffrey L; Dobrev, Dobromir; Wehrens, Xander H T

2015-09-01

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility.

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation

PubMed Central

Glasscock, Edward; Voigt, Niels; McCauley, Mark D.; Sun, Qiang; Li, Na; Chiang, David Y.; Zhou, Xiao-Bo; Molina, Cristina E.; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G.; Noebels, Jeffrey L.; Dobrev, Dobromir; Wehrens, Xander H. T.

2016-01-01

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson’s trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility. PMID:26162324

History of Asthma From Childhood and Arterial Stiffness in Asymptomatic Young Adults: The Bogalusa Heart Study.

PubMed

Sun, Dianjianyi; Li, Xiang; Heianza, Yoriko; Nisa, Hoirun; Shang, Xiaoyun; Rabito, Felicia; Kelly, Tanika; Harville, Emily; Li, Shengxu; He, Jiang; Bazzano, Lydia; Chen, Wei; Qi, Lu

2018-05-01

Asthma is related to various cardiovascular risk. Whether a history of asthma from childhood contributes to arterial stiffness in adulthood, a noninvasive surrogate for cardiovascular events, is unknown. Prospective analyses were performed among 1746 Bogalusa Heart Study participants aged 20 to 51 years with data on self-report asthma collected since childhood. Aorta-femoral pulse wave velocity (af-PWV, m/s) was repeatedly assessed among adults ≥aged 18 years. Generalized linear mixed models and generalized linear models were fitted for the repeated measurements of af-PWV and its changes between the last and the first measurements, respectively. After a median follow-up of 11.1 years, participants with a history of asthma from childhood had a higher af-PWV (6.78 versus 6.13; P =0.048) and a greater increase in af-PWV (8.99 versus 2.95; P =0.043) than those without asthma, adjusted for age, sex, race, smoking status, heart rate, body mass index, systolic blood pressure, lipids, and glycemia. In addition, we found significant interactions of asthma with body mass index and systolic blood pressure on af-PWV and its changes ( P for interaction <0.01). The associations of asthma with af-PWV and its changes appeared to be stronger among participants who were overweight and obese (body mass index ≥25 kg/m 2 ) or with prehypertension and hypertension (systolic blood pressure ≥120 mm Hg) compared with those with a normal body mass index or systolic blood pressure. Our findings indicate that a history of asthma from childhood is associated with higher af-PWV and greater increases in af-PWV, and such associations are stronger among young adults who are overweight or with elevated blood pressure. © 2018 American Heart Association, Inc.

Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial.

PubMed

Adabag, A Selcuk; Mithani, Salima; Al Aloul, Basel; Collins, Dorothea; Bertog, Stefan; Bloomfield, Hanna E

2009-05-01

Peroxisome proliferator-activated receptor alpha (PPARalpha) activators reduce inflammation and oxidative stress. Inflammation plays an important role in the initiation and maintenance of atrial fibrillation (AF). It has been suggested that PPARalpha activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARalpha activator gemfibrozil prevents or delays the development of AF in patients with coronary heart disease. We retrospectively analyzed the electrocardiograms (ECGs) performed in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial, a multicenter, randomized, double-blinded, secondary prevention trial of gemfibrozil and matching placebo. The ECGs were performed annually or biannually and when clinically indicated. Participants who were in AF on baseline ECG were excluded from the present analysis. Relative risk for AF was calculated from Cox regression with death as a competing risk factor. A total of 12,605 ECGs from 2,130 participants were interpreted (5.9 +/- 2.1 ECGs per participant, range 2-20). At baseline, the gemfibrozil (n = 1,070) and placebo (n = 1,060) groups were well matched. Mean age was 64.1 +/- 7.1 years. Over 4.4 +/- 1.5 years of follow-up, 123 (5.8%) participants developed new AF. There was no difference in AF incidence between the gemfibrozil and placebo groups (64/1,070 vs 59/1,060, respectively; P = .33). In Cox regression, the risk of AF was similar between the 2 study groups (hazard ratio 1.04, 95% CI 0.73-1.49, P = .82). In this post hoc analysis of a multicenter, double-blinded, randomized controlled trial, the PPARalpha activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease.

Attenuated response of L-type calcium current to nitric oxide in atrial fibrillation.

PubMed

Rozmaritsa, Nadiia; Christ, Torsten; Van Wagoner, David R; Haase, Hannelore; Stasch, Johannes-Peter; Matschke, Klaus; Ravens, Ursula

2014-03-01

Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF). Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.

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

PubMed

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

2013-09-01

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

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

PubMed

Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M

2014-02-01

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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%.

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.

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.

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.

Validation of PR interval length as a criterion for development of atrial fibrillation in non-Hispanic whites, African Americans and Hispanics.

PubMed

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

2015-01-01

PR interval prolongation on electrocardiogram (ECG) increases the risk of atrial fibrillation (AF). Non-Hispanic Whites are at higher risk of AF compared to African Americans and Hispanics. However, it remains unknown if prolongation of the PR interval for the development of AF varies by race/ethnicity. Therefore, we determined whether race affects the PR interval length's ability to predict AF and if the commonly used criterion of 200 ms in AF prediction models can continue to be used for non-White cohorts. This is a retrospective epidemiological study of consecutive inpatient and outpatients. An ECG database was initially interrogated. Patients were included if their initial ECG demonstrated sinus rhythm and had two or more electrocardiograms and declared a race and/or ethnicity as non-Hispanic White, African American or Hispanic. Development of AF was stratified by race/ethnicity along varying PR intervals. Cox models controlled for age, gender, race/ethnicity, systolic blood pressure, BMI, QRS, QTc, heart rate, murmur, treatment for hypertension, heart failure and use of AV nodal blocking agents to assess PR interval's predictive ability for development of AF. 50,870 patients met inclusion criteria of which 5,199 developed AF over 3.72 mean years of follow-up. When the PR interval was separated by quantile, prolongation of the PR interval to predict AF first became significant in Hispanic and African Americans at the 92.5th quantile of 196-201 ms (HR: 1.42, 95% CI: 1.09-1.86, p=0.01; HR: 1.32, 95% CI: 1.07-1.64, p=0.01, respectively) then in non-Hispanic Whites at the 95th quantile at 203-212 ms (HR: 1.24, 95% CI: 1.24-1.53, p=0.04). For those with a PR interval above 200 ms, African Americans had a lower risk than non-Hispanic Whites to develop AF (HR: 0.80, 95% CI: 0.64-0.95, p=0.012), however, no significant difference was demonstrated in Hispanics. This is the first study to validate a PR interval value of 200 ms as a criterion in African Americans and Hispanics for the development of AF. However, a value of 200 ms may be less sensitive as a predictive measure for the development of AF in African Americans compared to non-Hispanic Whites. Copyright © 2015 Elsevier Inc. All rights reserved.

The QT Interval and Risk of Incident Atrial Fibrillation

PubMed Central

Mandyam, Mala C.; Soliman, Elsayed Z.; Alonso, Alvaro; Dewland, Thomas A.; Heckbert, Susan R.; Vittinghoff, Eric; Cummings, Steven R.; Ellinor, Patrick T.; Chaitman, Bernard R.; Stocke, Karen; Applegate, William B.; Arking, Dan E.; Butler, Javed; Loehr, Laura R.; Magnani, Jared W.; Murphy, Rachel A.; Satterfield, Suzanne; Newman, Anne B.; Marcus, Gregory M.

2013-01-01

BACKGROUND Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine. OBJECTIVE To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF. METHODS We examined a prolonged QT corrected by the Framingham formula (QTFram) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (Health ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by other formulae. RESULTS Among 14,538 ARIC participants, a prolonged QTFram predicted a roughly two-fold increased risk of AF (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.42–2.96, p<0.001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in CHS and Health ABC and were similar across various QT correction methods. Also in ARIC, each 10-ms increase in QTFram was associated with an increased unadjusted (HR 1.14, 95%CI 1.10–1.17, p<0.001) and adjusted (HR 1.11, 95%CI 1.07–1.14, p<0.001) risk of AF. Findings regarding a short QT were inconsistent across cohorts. CONCLUSIONS A prolonged QT interval is associated with an increased risk of incident AF. PMID:23872693

CXCL6 (Granulocyte Chemotactic Protein-2): a novel chemokine involved in the innate immune response of the amniotic cavity

PubMed Central

Mittal, Pooja; Romero, Roberto; Kusanovic, Juan Pedro; Edwin, Samuel S.; Gotsch, Francesca; Mazaki-Tovi, Shali; Espinoza, Jimmy; Erez, Offer; Nhan-Chang, Chia-Ling; Than, Nandor G; Vaisbuch, Edi; Hassan, Sonia S

2008-01-01

PROBLEM CXCL6 is a potent pro-inflammatory neutrophil chemoattractant and activator whose activity during pregnancy is not well-established. The purpose of this study was to determine if CXCL6 is present in amniotic fluid (AF) and if CXCL6 concentrations in AF change with labor (preterm and term) or intra-amniotic infection/inflammation (IAI). METHOD OF STUDY A cross-sectional study was conducted with the following groups: 1) mid-trimester (n=65); 2) term no labor (n=20); 3) term labor (n=44); 4) patients with PTL with subsequent term delivery (n=57); 5) preterm labor (PTL) without IAI who delivered preterm (n=47); and 6) PTL with IAI (n=62). AF CXCL6 concentrations were determined by ELISA. RESULTS CXCL6 was present in all term samples, but undetectable in 64/65 mid-trimester specimens. Patients with PTL and IAI had a significantly higher median CXCL6 AF concentration than those with PTL without IAI [228.9 pg/ml (0.0–8344.8) vs. 55.7 pg/ml (0–454.4); p<0.05] and those with PTL and term delivery [41.5 pg/ml (0–279.0); p<0.05]. Median AF CXCL6 concentration did not change with spontaneous term labor [term no labor: 81.1 pg/ml (8.5–201.7) vs. term labor: 75.2 pg/ml (6.7–378.7): p=0.74]. CONCLUSIONS 1) CXCL6 is detectable in AF and its concentration increases with gestational age; 2) IAI results in increased CXCL6 AF concentrations, suggesting that CXCL6 plays a role in the deployment of an inflammatory response; 3) In contrast to related chemokines, specifically IL-8, AF CXCL6 does not appear to be involved in spontaneous term parturition. These observations are novel, and suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity. PMID:18782286

Atrial fibrillation in immigrant groups: a cohort study of all adults 45 years of age and older in Sweden.

PubMed

Wändell, Per; Carlsson, Axel C; Li, Xinjun; Gasevic, Danijela; Ärnlöv, Johan; Holzmann, Martin J; Sundquist, Jan; Sundquist, Kristina

2017-09-01

To study the association between country of birth and incident atrial fibrillation (AF) in several immigrant groups in Sweden. The study population included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was defined as having at least one registered diagnosis of AF in the National Patient Register. The incidence of AF in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence intervals (CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status. Compared to their Swedish-born counterparts, higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74 (1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67-2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05-1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men (HRs ≤ 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain), Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon and Iran), and among women from Nordic countries (except Finland), Southern Europe, Western Europe (except Germany), Africa, North America, Latin America, Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion, we observed substantial differences in incidence of AF between immigrant groups and the Swedish-born population. A greater awareness of the increased risk of AF development in some immigrant groups may enable for a timely diagnosis, treatment and prevention of its debilitating complications, such as stroke.

Antiferromagnetic vs. non-magnetic ε phase of solid oxygen. Periodic density functional theory studies using a localized atomic basis set and the role of exact exchange.

PubMed

Ramírez-Solís, A; Zicovich-Wilson, C M; Hernández-Lamoneda, R; Ochoa-Calle, A J

2017-01-25

The question of the non-magnetic (NM) vs. antiferromagnetic (AF) nature of the ε phase of solid oxygen is a matter of great interest and continuing debate. In particular, it has been proposed that the ε phase is actually composed of two phases, a low-pressure AF ε 1 phase and a higher pressure NM ε 0 phase [Crespo et al., Proc. Natl. Acad. Sci. U. S. A., 2014, 111, 10427]. We address this problem through periodic spin-restricted and spin-polarized Kohn-Sham density functional theory calculations at pressures from 10 to 50 GPa using calibrated GGA and hybrid exchange-correlation functionals with Gaussian atomic basis sets. The two possible configurations for the antiferromagnetic (AF1 and AF2) coupling of the 0 ≤ S ≤ 1 O 2 molecules in the (O 2 ) 4 unit cell were studied. Full enthalpy-driven geometry optimizations of the (O 2 ) 4 unit cells were done to study the pressure evolution of the enthalpy difference between the non-magnetic and both antiferromagnetic structures. We also address the evolution of structural parameters and the spin-per-molecule vs. pressure. We find that the spin-less solution becomes more stable than both AF structures above 50 GPa and, crucially, the spin-less solution yields lattice parameters in much better agreement with experimental data at all pressures than the AF structures. The optimized AF2 broken-symmetry structures lead to large errors of the a and b lattice parameters when compared with experiments. The results for the NM model are in much better agreement with the experimental data than those found for both AF models and are consistent with a completely non-magnetic (O 2 ) 4 unit cell for the low-pressure regime of the ε phase.

U2AF1 mutations alter splice site recognition in hematological malignancies.

PubMed

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

2015-01-01

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

Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis

PubMed Central

Shirazi, Fazal; Ferreira, Jose A. G.; Stevens, David A.; Clemons, Karl V.; Kontoyiannis, Dimitrios P.

2016-01-01

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation. PMID:26930399

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

PubMed

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

2014-08-21

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

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

PubMed

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

2016-06-01

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

Lipid metabolism of commercial layers fed diets containing aflatoxin, fumonisin, and a binder.

PubMed

Siloto, E V; Oliveira, E F A; Sartori, J R; Fascina, V B; Martins, B A B; Ledoux, D R; Rottinghaus, G E; Sartori, D R S

2013-08-01

Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers, leading to huge economic losses. This experiment was conducted to determine the effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in combination, on the lipid metabolism in commercial layers and investigate the efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were randomized into a 3 × 2 + 1 factorial arrangement (3 diets with no binder containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU; and a control diet with no mycotoxins and binders), totaling 7 treatments. The hens contaminated with AF showed the characteristic effects of aflatoxicosis, such as a yellow liver, resulting from the accumulation of liver fat, lower values of plasma very low-density lipoprotein and triglycerides, and higher relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of FU were not observed in this study. On the other hand, the FU caused a reduction in small intestine length and an increase in abdominal fat deposition. The glucan-based binder prevented some of the deleterious effects of these mycotoxins, particularly the effects of AF on hepatic lipid metabolism, kidney relative weight, and FU in the small intestine.

Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis.

PubMed

Shirazi, Fazal; Ferreira, Jose A G; Stevens, David A; Clemons, Karl V; Kontoyiannis, Dimitrios P

2016-01-01

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation.

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

PubMed

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

2016-07-27

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

Using the Public Involvement Impact Assessment Framework to assess the impact of public involvement in a mental health research context: A reflective case study.

PubMed

Collins, Michelle; Long, Rita; Page, Anthony; Popay, Jennie; Lobban, Fiona

2018-04-25

We assess the utility of the Public Involvement Impact Assessment Framework (PiiAF) as a resource to support research teams in assessing the impact of Public Involvement across diverse research and public involvement (PI) contexts. PiiAF was developed in response to a well-documented growth in Public Involvement in health research in the United Kingdom that demands a more sophisticated evidence base to demonstrate its impact. We used a reflective case study approach drawing on contemporaneous meeting notes, PiiAF website resources and retrospective reflections to describe how PiiAF helped us to develop an impact assessment plan of the PI in a university-based mental health research centre. We consider key aspects of our experiences of using PiiAF as a tool to help us design an impact assessment of PI, interpret these experiences with reference to relevant theory and research and share insights that may be useful to other teams considering using PiiAF. These insights include understanding the commitment of time and effort required to develop effective PI impact assessment plans; the flexibility of PiiAF and its ability to be used in a range of research and PI contexts; and the advantages of involving all stakeholders (including the public) in the development of an PI assessment plan. © 2018 The Authors. Health Expectations published by John Wiley & Sons Ltd.

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

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

Yang, Baode; Li, Chenxing

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I{submore » Kv1.5}) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I{sub hERG}). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I{sub Kir2.1}). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I{sub Kv1.5} and I{sub hERG}, which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.« less

Anisotropy-governed competition of magnetic phases in the honeycomb quantum magnet Na3Ni2SbO6 studied by dilatometry and high-frequency ESR

NASA Astrophysics Data System (ADS)

Werner, J.; Hergett, W.; Gertig, M.; Park, J.; Koo, C.; Klingeler, R.

2017-06-01

Thermodynamic properties and low-energy magnon excitations of S =1 honeycomb-layered Na3Ni2SbO6 have been investigated by high-resolution dilatometry, static magnetization, and high-frequency electron spin resonance studies in magnetic fields up to 16 T. At TN = 16.5 K, there is a tricritical point separating two distinct antiferromagnetic phases, AF1 and AF2, from the paramagnetic regime. In addition, our data imply short-range antiferromagnetic correlations at least up to ˜5 TN . Well below TN, the magnetic field BC1≈9.5 T is needed to stabilize AF2 against AF1. The thermal expansion and magnetostriction anomalies at TN and BC 1 imply significant magnetoelastic coupling, both of which are associated with a sign change of ∂ L /∂ B . The transition at BC 1 is associated with softening of the antiferromagnetic resonance modes observed in the electron-spin-resonance spectra. The anisotropy gap Δ =360 GHz implies considerable uniaxial anisotropy. We deduce the crucial role of axial anisotropy favoring the AF1 spin structure over the AF2 one. While the magnetostriction data disprove a simple spin-flop scenario at BC 1, the nature of a second transition at BC 2 ≈ 13 T remains unclear. Both the sign of the magnetostriction and Grüneisen analysis suggest that the short-range correlations at high temperatures are of AF2 type.

Echocardiographic predictors of atrial fibrillation recurrence after catheter ablation: A literature review.

PubMed

Liżewska-Springer, Aleksandra; Dąbrowska-Kugacka, Alicja; Lewicka, Ewa; Drelich, Łukasz; Królak, Tomasz; Raczak, Grzegorz

2018-06-20

Catheter ablation (CA) is a well-known treatment option for patients with symptomatic drug-resistant atrial fibrillation (AF). Multiple factors have been identified to determine AF recurrence after CA, however their predictive value is rather small. Identification of novel predictors of CA outcome is therefore of primary importance to reduce health costs and improve long-term results of this intervention. The recurrence of AF following CA is related to the severity of left ventricular (LV) dysfunction, extend of atrial dilatation and fibrosis. The aim of this paper was to present and discuss the latest studies on utility of echocardiographic parameters in terms of CA effectiveness in patients with paroxysmal and persistent AF. PubMed, Google Scholar, EBSCO databases were searched for studies reporting echocardiographic preprocedural predictors of AF recurrence after CA. LV systolic and diastolic function, as well as atrial size, strain and dyssynchrony were taken into consideration. Twenty one full-text articles were analyzed, including three meta-analyses. Several echocardiographic parameters have been reported to determine a risk of AF recurrence after CA. There are conventional methods that measure left atrial (LA) size and volume, LV ejection fraction, parameters assessing LV diastolic dysfunction, and methods using more innovative technologies based on speckle tracking echocardiography (STE) to determine LA synchrony and strain. Each of these parameters has its own predictive value. Regarding CA effectiveness, every patient has to be evaluated individually to estimate the risk of AF recurrence, optimally using a combination of several echocardiographic parameters.

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.

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.

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.

Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation.

PubMed

Schnabel, Renate B; Maas, Renke; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Levy, Daniel; Ellinor, Patrick T; Lubitz, Steven A; McManus, David D; Magnani, Jared W; Atzler, Dorothee; Böger, Rainer H; Schwedhelm, Edzard; Vasan, Ramachandran S; Benjamin, Emelia J

2016-06-01

Oxidative stress plays an important role in the development of atrial fibrillation (AF). Arginine derivatives including asymmetric dimethylarginine (ADMA) are central to nitric oxide metabolism and nitrosative stress. Whether blood concentrations of arginine derivatives are related to incidence of AF is uncertain. In 3,310 individuals (mean age 58 ± 10 years, 54% women) from the community-based Framingham Study, we prospectively examined the relations of circulating levels of ADMA, l-arginine, symmetric dimethylarginine (SDMA), and the ratio of l-arginine/ADMA to incidence of AF using proportional hazards regression models. Over a median follow-up time of 10 years, 247 AF cases occurred. Using age- and sex-adjusted regression models, ADMA was associated with a hazard ratio of 1.15 per 1-SD increase in loge-biomarker concentration (95% CI 1.02-1.29, P = .02) for AF, which was no longer significant after further risk factor adjustment (hazard ratio 1.09, 95% CI 0.97-1.23, P = .15). Neither l-arginine nor SDMA was related to new-onset AF. A clinical model comprising clinical risk factors for AF (for age, sex, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, diabetes, hypertension treatment, myocardial infarction, and heart failure; c statistic = 0.781; 95% CI 0.753-0.808) was not improved by the addition of ADMA (0.782; 95% CI 0.755-0.809). Asymmetric dimethylarginine and related arginine derivatives were not associated with incident AF in the community after accounting for other clinical risk factors and confounders. Its role in the pathogenesis of AF needs further refinement. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation.

PubMed

Zaman, Junaid A B; Sauer, William H; Alhusseini, Mahmood I; Baykaner, Tina; Borne, Ryan T; Kowalewski, Christopher A B; Busch, Sonia; Zei, Paul C; Park, Shirley; Viswanathan, Mohan N; Wang, Paul J; Brachmann, Johannes; Krummen, David E; Miller, John M; Rappel, Wouter Jan; Narayan, Sanjiv M; Peters, Nicholas S

2018-01-01

The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation. We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum -dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms. Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation. © 2018 American Heart Association, Inc.

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

PubMed

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

2017-04-01

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

Electrocardiographic Predictors of Incident Atrial Fibrillation

PubMed Central

Nguyen, Kaylin T.; Vittinghoff, Eric; Dewland, Thomas A.; Mandyam, Mala C.; Stein, Phyllis K.; Soliman, Elsayed Z.; Heckbert, Susan R.; Marcus, Gregory M.

2017-01-01

Atrial fibrillation (AF) is likely secondary to multiple different pathophysiological mechanisms that are increasingly, but incompletely understood. Motivated by the hypothesis that 3 previously described electrocardiographic (ECG) predictors of AF identify distinct AF mechanisms, we sought to determine if these ECG findings independently predict incident disease. Among Cardiovascular Health Study participants without prevalent AF, we determined whether left anterior fascicular block (LAFB), a prolonged QTC, and atrial premature complexes (APCs) each predicted AF after adjusting for each other. We then calculated the attributable risk in the exposed for each ECG marker. LAFB and QTC intervals were assessed on baseline 12-lead ECG (n=4,696). APC count was determined using 24-hour Holter recordings obtained in a random subsample (n=1,234). After adjusting for potential confounders and each ECG marker, LAFB (hazard ratio [HR. 2.1, 95% confidence interval [CI. 1.1–3.9, p=0.023), a prolonged QTC (HR 2.5, 95% CI 1.4–4.3, p=0.002), and every doubling of APC count (HR 1.2, 95% CI 1.1–1.3, p<0.001) each remained independently predictive of incident AF. The attributable risk of AF in the exposed was 35% (95% CI 13–52%) for LAFB, 25% (95% CI 0.6–44%) for a prolonged QTC, and 34% (95% CI 26–42%) for APCs. In conclusion, in a community-based cohort, 3 previously established ECG-derived AF predictors were each independently associated with incident AF, suggesting they may represent distinct mechanisms underlying the disease. PMID:27448684

Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid.

PubMed

Sanie-Jahromi, Fatemeh; Ahmadieh, Hamid; Soheili, Zahra-Soheila; Davari, Maliheh; Ghaderi, Shima; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Deezagi, Abdolkhalegh; Pakravesh, Jalil; Bagheri, Abouzar

2012-04-10

Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers) during treatment of human retinal pigment epithelium (RPE) cells with amniotic fluid (AF), RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1) confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

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.

Recovery of injured arcuate fasciculus in the dominant hemisphere in a patient with an intracerebral hemorrhage.

PubMed

Jang, Sung Ho; Lee, Han Do

2014-12-01

This study reports on a patient with an intracerebral hemorrhage who showed recovery of an injured arcuate fasciculus (AF) in the dominant hemisphere, using follow-up diffusion tensor tractography. A 43-year-old right-handed man presented with severe aphasia and hemiparesis resulting from a spontaneous intracerebral hemorrhage in the left parietotemporal lobes. The patient showed severe aphasia at 1 month after onset, with an aphasia quotient of 5% on the Korean-Western Aphasia Battery. He underwent comprehensive rehabilitative therapy until 22 months after onset and his aphasia showed improvement, with an aphasia quotient of 58% on the Korean-Western Aphasia Battery. On 1-month diffusion tensor tractography, only the thin ascending part of the left AF from the Wernicke area remained. In contrast, on 16-month diffusion tensor tractography, the injured left AF was thickened and elongated to around the left Broca area; however, discontinuation of the left AF was observed around the left Broca area, and this continuation was elongated to the left Broca area on 22-month diffusion tensor tractography. This study reports on a patient who showed recovery from injury of the left AF along with improvement of aphasia. Recovery of the injured AF in the dominant hemisphere appears to be one of the mechanisms for recovery from aphasia.

Barriers and Facilitators Related to Participation in Aquafitness Programs for People with Multiple Sclerosis

PubMed Central

Kitchen, Kaitlyn; Nicoll, Kaley

2012-01-01

Exercise and leisure activities provide physical and psychosocial benefits to people with multiple sclerosis (MS) and can enhance their quality of life. In Winnipeg, Manitoba, Canada, people with MS have reported barriers to their participation in local MS-specific aquafitness (AF) programs. Therefore, a formal exploration of the accessibility of local AF programs for people with MS was undertaken. The purpose of this phenomenological study was to identify factors that facilitate or impede participation in AF programs by individuals with MS living in Winnipeg. Qualitative data were collected from a total of eight participants through one focus group (n = 7) and one in-depth interview (n = 1). The sample consisted of individuals with MS who were currently participating in AF programming as well as those who were not. Data were audio-recorded and transcribed verbatim, and thematic analysis was completed. Seven themes emerged regarding factors affecting participation in local AF programs. Barriers to participation included inadequate transportation, lack of one-on-one support, environmental inaccessibility, and fears associated with participation in the programs. Facilitators of participation included a knowledgeable instructor and experiencing physical and psychosocial benefits from the program. Information from this study was used locally to advocate for people with MS in order to increase participation in local AF programming. PMID:24453744

The effects of the activation of the inner-hair-cell basolateral K+ channels on auditory nerve responses.

PubMed

Altoè, Alessandro; Pulkki, Ville; Verhulst, Sarah

2018-07-01

The basolateral membrane of the mammalian inner hair cell (IHC) expresses large voltage and Ca 2+ gated outward K + currents. To quantify how the voltage-dependent activation of the K + channels affects the functionality of the auditory nerve innervating the IHC, this study adopts a model of mechanical-to-neural transduction in which the basolateral K + conductances of the IHC can be made voltage-dependent or not. The model shows that the voltage-dependent activation of the K + channels (i) enhances the phase-locking properties of the auditory fiber (AF) responses; (ii) enables the auditory nerve to encode a large dynamic range of sound levels; (iii) enables the AF responses to synchronize precisely with the envelope of amplitude modulated stimuli; and (iv), is responsible for the steep offset responses of the AFs. These results suggest that the basolateral K + channels play a major role in determining the well-known response properties of the AFs and challenge the classical view that describes the IHC membrane as an electrical low-pass filter. In contrast to previous models of the IHC-AF complex, this study ascribes many of the AF response properties to fairly basic mechanisms in the IHC membrane rather than to complex mechanisms in the synapse. Copyright © 2018 Elsevier B.V. All rights reserved.

Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII

PubMed Central

Kubaski, Francyne; Brusius-Facchin, Ana Carolina; Mason, Robert W.; Patel, Pravin; Burin, Maira G.; Michelin-Tirelli, Kristiane; Kessler, Rejane Gus; Bender, Fernanda; Leistner-Segal, Sandra; Moreno, Carolina A.; Cavalcanti, Denise P.; Giugliani, Roberto; Tomatsu, Shunji

2017-01-01

Objective The aim of this study was to quantify GAGs in amniotic fluid (AF) from an MPS VII fetus compared with age-matched fetuses obtained from normal pregnancies. Method Disaccharides were measured by liquid chromatography tandem mass spectrometry (LC/MS/MS), compared to age-matched controls. Enzyme assay was performed in AF supernatant or cultured amniocytes. GUSB was analyzed by next generation sequencing using Ion Torrent Personal Genome Machine with a customized panel. Results No activity of β-glucuronidase was detected in fetal cells. The pregnancy was spontaneously terminated in the third trimester. Genetic studies identified a homozygous mutation of p.N379D (c.1135A>G) in the GUSB gene. LC/MS/MS showed that chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate levels were markedly increased in the MPS VII AF, compared to those in age-matched control AF (DS, HS, and C6S more than 10 × than age-matched controls; C4S and KS more than 3 times higher). Conclusion This is the first report of specific GAG analysis in AF from an MPS VII fetus, indicating that GAG elevation in AF occurs by 21 weeks of gestation and could be an additional tool for prenatal diagnosis of MPS VII and potentially other MPS types. PMID:28207930

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation.

PubMed

Yang, Baode; Li, Chenxing; Sun, Junyi; Wang, Xinghui; Liu, Xinling; Yang, Chun; Chen, Lina; Zhou, Jun; Hu, Hao

2017-05-01

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I Kv1.5 ) were markedly inhibited by 12.5-50.0mM ethanol in a concentration-dependent manner. Ethanol with 50.0mM could inhibit rapid delayed rectifier potassium currents (I hERG ). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (I Kir2.1 ). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I Kv1.5 and I hERG , which contributed to preventing the development and duration of AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Simulation of Spiral Waves and Point Sources in Atrial Fibrillation with Application to Rotor Localization

PubMed Central

Ganesan, Prasanth; Shillieto, Kristina E.; Ghoraani, Behnaz

2018-01-01

Cardiac simulations play an important role in studies involving understanding and investigating the mechanisms of cardiac arrhythmias. Today, studies of arrhythmogenesis and maintenance are largely being performed by creating simulations of a particular arrhythmia with high accuracy comparable to the results of clinical experiments. Atrial fibrillation (AF), the most common arrhythmia in the United States and many other parts of the world, is one of the major field where simulation and modeling is largely used. AF simulations not only assist in understanding its mechanisms but also help to develop, evaluate and improve the computer algorithms used in electrophysiology (EP) systems for ablation therapies. In this paper, we begin with a brief overeview of some common techniques used in simulations to simulate two major AF mechanisms – spiral waves (or rotors) and point (or focal) sources. We particularly focus on 2D simulations using Nygren et al.’s mathematical model of human atrial cell. Then, we elucidate an application of the developed AF simulation to an algorithm designed for localizing AF rotors for improving current AF ablation therapies. Our simulation methods and results, along with the other discussions presented in this paper is aimed to provide engineers and professionals with a working-knowledge of application-specific simulations of spirals and foci. PMID:29629398

Magnetoresistance measurements in Ferro -- Antiferromagnetic bilayers based on the Ca-doped lanthanum manganite system

NASA Astrophysics Data System (ADS)

Gomez, M. E.; Marin, L.; Ramirez, G.; Prieto, P.

2011-03-01

We studied the isothermal magnetic field dependence of the resistance behavior in ferromagnetic--antiferromagnetic interface based on the Ca-doped lanthanum manganite system at temperatures below Neel temperature of the antiferromagnetic layer. We studied the influence of the thickness of the AF-layer, tAF , and F-layer, tF , on the ZFC and FC magnetoresistance (MR) in La 2/3 Ca 1/3 Mn O3 (tF) / La 1/3 Ca 2(3 Mn O3 (tAF) bilayers. HFC was 400 Oe and the applied magnetic field, H. We systematically varied the tF and tAF thickness, maintaining constant the total bilayer thickness (d = tF +tAF) . We found that MR has hysteretic behavior as observed in [ La 2/3 Ca 1/3 Mn O3 (tF) / La 1/3 Ca 2(3 Mn O3 (tAF) ]N superlattices, but; MR increases with the increasing field from H=0 to a maximum and then decreases continuously. This behavior also appears for negative fields in both ZFC and FC loops. The position and magnitude of the maximum is not symmetric with respect to the axis H=0. Work supported by CENM-COLCIENCIAS contract RC-0043-(2005).

Do Women With Atrial Fibrillation Experience More Severe Strokes? Results From the Austrian Stroke Unit Registry.

PubMed

Lang, Clemens; Seyfang, Leonhard; Ferrari, Julia; Gattringer, Thomas; Greisenegger, Stefan; Willeit, Karin; Toell, Thomas; Krebs, Stefan; Brainin, Michael; Kiechl, Stefan; Willeit, Johann; Lang, Wilfried; Knoflach, Michael

2017-03-01

Ischemic strokes associated with atrial fibrillation (AF) are more severe than those of other cause. We aim to study potential sex effects in this context. In this cross-sectional study, 74 425 adults with acute ischemic stroke from the Austrian Stroke Unit Registry were included between March 2003 and January 2016. In 63 563 patients, data on the National Institutes of Health Stroke Scale on admission to the stroke unit, presence of AF, vascular risk factors, and comorbidities were complete. Analysis was done by a multivariate regression model. Stroke severity in general increased with age. AF-related strokes were more severe than strokes of other causes. Sex-related differences in stroke severity were only seen in stroke patients with AF. Median (Q 25 , 75 ) National Institutes of Health Stroke Scale score points were 9 (4,17) in women and 6 (3,13) in men ( P <0.001). The interaction between AF and sex on stroke severity was independent of age, previous functional status, vascular risk factors, and vascular comorbidities and remained significant in various subgroups. Women with AF do not only have an increased risk of stroke when compared with men but also experience more severe strokes. © 2017 American Heart Association, Inc.

A review of apixaban for stroke prevention in atrial fibrillation: insights from ARISTOTLE.

PubMed

Hess, Connie N; Al-Khatib, Sana M; Granger, Christopher B; Lopes, Renato

2013-09-01

Atrial fibrillation (AF) is associated with significant mortality and morbidity, and stroke represents the most-feared complication. Consequently, AF treatment has focused on thromboprophylaxis, with warfarin as the mainstay of therapy. However, concerns over ease of use and safety have limited its use. Three novel oral anticoagulants have been approved for use in stroke prevention in AF based on randomized data: 1) dabigatran, studied in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY); 2) rivaroxaban, studied in Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF); and 3) apixaban, studied in Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). In this review, we focus on apixaban and discuss subgroup analyses that have been performed in the three trials comparing novel oral anticoagulants with warfarin. We conclude with recommendations regarding further investigations.

Effects of radial compression on a novel simulated intervertebral disc-like assembly using bone marrow-derived mesenchymal stem cell cell-sheets for annulus fibrosus regeneration.

PubMed

See, Eugene Yong-Shun; Toh, Siew Lok; Goh, James Cho-Hong

2011-10-01

The aim of this study was to develop a tissue engineering approach in regenerating the annulus fibrosus (AF) as part of an overall strategy to produce a tissue-engineered intervertebral disc (IVD) replacement. To determine whether a rehabilitative simulation regime on bone marrow–derived mesenchymal stem cell cell-sheet is able to aid the regeneration of the AF. No previous study has used bone marrow–derived mesenchymal stem cell cell-sheets simulated by a rehabilitative regime to regenerate the AF. The approach was to use bone marrow–derived stem cells to form cell-sheets and incorporating them onto silk scaffolds to simulate the native lamellae of the AF. The in vitro experimental model used to study the efficacy of such a system was made up of the tissue engineering AF construct wrapped around a silicone disc to form a simulated IVD-like assembly. The assembly was cultured within a custom-designed bioreactor that provided a compressive mechanical stimulation onto the silicone disc. The silicone nucleus pulposus would bulge radially and compress the simulated AF to mimic the physiological conditions. The simulated IVD-like assembly was compressed using a rehabilitative regime that lasted for 4 weeks at 0.25 Hz, for 15 minutes each day. With the rehabilitative regime, the cell-sheets remained viable but showed a decrease in cell numbers and viability. Gene expression analysis showed significant upregulation of IVD-related genes and there was an increased ratio of collagen type II to collagen type I found within the extracellular matrix. The results suggested that a rehabilitative regime caused extensive remodeling to take place within the simulated IVD-like assembly, producing extracellular matrix similar to that found in the inner AF.

Non-selective His bundle pacing with a biphasic waveform: enhancing septal resynchronization.

PubMed

Ortega, Daniel F; Barja, Luis D; Logarzo, Emilio; Mangani, Nicolas; Paolucci, Analia; Bonomini, Maria P

2018-05-01

His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P < 0.0005) while RVA significantly increased QRS duration (SR: 169 ms vs. RVA: 198 ms, P < 0.05) and did not change RLVT (P = NS). Consistently, IVCT moderately decreased under AF-nHB (SR: 238 ms vs. RVA: 184 ms, P < 0.05 vs. SR) and dP/dtmax showed a 93.35 [mmHg] average increase under AF-nHB against SR. Also, T-wave inversions were observed during AF-nHB immediately after SR and RVA pacing suggesting the occurrence of cardiac memory. AF-nHB corrected bundle branch blocks in patients with severe conduction disturbances, even in those with dilated cardiomiopathy, outstanding from RVA. Also, the occurrence of cardiac memory during AF-nHB turned up as an observational finding of this study.

Erectile Dysfunction Is Not a Predictor of Atrial Fibrillation: A Population-Based Propensity-Score Matched Cohort Study.

PubMed

Liu, Kuan-Liang; Ye, Ling-Long; Chou, Shing-Hsien; Tung, Ying-Chang; Lin, Yu-Sheng; Wu, Lung-Sheng; Lin, Chia-Pin; Shia, Ben-Chang; Chu, Pao-Hsien

2016-01-01

Erectile dysfunction (ED) has been regarded a marker of cardiovascular diseases. Nevertheless, the association between ED and incident atrial fibrillation (AF) remains unknown. To determine the association between ED and incident AF. This population-based cohort study was conducted using the National Health Insurance Research Database in Taiwan. In total, 6,273 of patients with ED without a prior diagnosis of AF were enrolled from January 1, 2001 through December 31, 2009, and a propensity-score matching method was used to identify 3,516 patients in the ED and control groups. Newly incident AF at follow-up was recorded as the end point. The mean age of the study population was 40.0 ± 17.1 years, and the follow-up period was 8.0 ± 0.5 years. Compared with the control group, patients with ED were older and had more of the following comorbidities: D'Hoore Charlson Comorbidity Index, hypertension, congestive heart failure, diabetes mellitus, dyslipidemia, chronic kidney disease, coronary artery disease, stroke, chronic lung disease, major depression disorder, obstructive sleep apnea, and hyperthyroidism. After adjusting for confounders, the ED group was not associated with more incident AF compared with the control group (hazard ratio = 1.031, 95% confidence interval = 0.674-1.578, P =.888). In these patients, ED of an organic origin was associated with a trend of having AF more often compared with ED of a psychosexual type (P =.272 by log-rank test). Although ED is known as a predictor of atherosclerotic cardiovascular diseases, it is not independently associated with incident AF in men. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Socio-demographic determinants of aflatoxin B1-lysine adduct levels among pregnant women in Kumasi, Ghana.

PubMed

Shuaib, F M B; Jolly, P E; Ehiri, J E; Ellis, W O; Yatich, N J; Funkhouser, E; Person, S D; Williams, J H; Qian, G; Wang, J-S

2012-12-01

Aflatoxins are fungal metabolites that contaminate staple food crops in many developing countries. Although studies have linked these toxins to adverse birth outcomes and poor infant development, no study has investigated the socio-demographic and economic determinants of aflatoxin levels among pregnant women living in sub-Saharan Africa. A cross-sectional study was conducted among 785 pregnant women in Kumasi. Aflatoxin B1 lysine adduct levels (AF-ALB) were determined by High Performance Liquid Chromatography. Analysis of variance was used to determine mean log AF-ALB levels and significance of differences in these levels according to socio-demographic variables. Logistic regression was used to identify independent associations of socio-demographics with having AF-ALB levels (≥ 11.34 pg/mg; upper quartile). AF-ALB levels ranged from 0.44 pg/mg to 268.73 pg/mg albumin with a median level of 5.0 pg/mg. Bivariate analyses indicates that mean ln AF-ALB as well as the percent of women having high AF-ALB levels (≥ 11.34 pg/mg; upper quartile) were inversely associated with indices of higher socioeconomic status: higher education and income, being employed and having a flush toilet. Higher income, being employed, having one child (verses no children) and having a flush toilet (verses no toilet facilities) were each independently associated with a 30-40% reduced odds of high AF-ALB levels. Additional research is needed to investigate how socio-demographic and economic factors interact to influence aflatoxin ingestion by individuals in regions with high aflatoxin crop contamination. This knowledge can be used to formulate and implement policies that will reduce exposure of women and their unborn children to these toxins.

The cost of atrial fibrillation in Italy: a five-year analysis of healthcare expenditure in the general population. From the Italian Survey of Atrial Fibrillation Management (ISAF) study.

PubMed

Zoni Berisso, M; Landolina, M; Ermini, G; Parretti, D; Zingarini, G L; Degli Esposti, L; Cricelli, C; Boriani, G

2017-01-01

Atrial fibrillation (AF) is a relevant item of expenditure for the National Healthcare systems. The aim of the study was to estimate the annual costs of AF in Italy. The Italian Survey of Atrial Fibrillation Management Study enrolled 6.036 patients with AF among 295.906 subjects representative of the Italian population. Data were collected by 233 General Practitioners (GPs) distributed across Italy. Quantities of resources used during the 5 years preceding the ISAF screening were inferred from the survey data and multiplied by the current Italian unit costs of 2015 in order to estimate the mean per patient annual cumulative cost of AF. Patients were subdivided on the basis of the number of hospitalizations, invasive/non-invasive diagnostic tests and invasive therapeutic procedures in 3 different clinical subsets: "low cost", " medium cost" and "high cost clinical scenario". The estimated mean costs per patient per year were 613 €, 891 € and 1213 € for the "Low cost", "Medium cost" and "High Cost Clinical Scenario" respectively. Hospitalizations and inpatient interventional procedures accounted for more than 80% of the cumulative annual costs. The mean annual costs among patients pursuing "Rhythm control" strategy was 956 €. In Italy, the estimated costs of AF per patient per year are lower than those reported in other developed countries and vary widely related to the different characteristics of AF patients. Hospitalizations and interventional procedures are the main drivers of costs. The mean annual cost of AF is mainly influenced by the duration of the period of observation and the patients' characteristics. Measures to reduce hospitalizations are needed.

Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00075467 modulates atrial electrical remodeling by sponging miR-328 to regulate CACNA1C.

PubMed

Li, Zhan; Wang, Ximin; Wang, Weizong; Du, Juanjuan; Wei, Jinqiu; Zhang, Yong; Wang, Jiangrong; Hou, Yinglong

2017-07-01

Electrical remodeling has been reported to play a major role in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) have been increasingly recognized as contributors to the pathology of heart diseases. However, the roles and mechanisms of lncRNAs in electrical remodeling during AF remain unknown. In this study, the lncRNA expression profiles of right atria were investigated in AF and non-AF rabbit models by using RNA sequencing technique and validated using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 99,843 putative new lncRNAs were identified, in which 1220 differentially expressed transcripts exhibited >2-fold change. Bioinformatics analysis was conducted to predict the functions and interactions of the aberrantly expressed genes. On the basis of a series of filtering pipelines, one lncRNA, TCONS_00075467, was selected to explore its effects and mechanisms on electrical remodeling. The atrial effective refractory period was shortened in vivo and the L-type calcium current and action potential duration were decreased in vitro by silencing of TCONS_00075467 with lentiviruses. Besides, the expression of miRNA-328 was negatively correlated with TCONS_00075467. We further demonstrated that TCONS_00075467 could sponge miRNA-328 in vitro and in vivo to regulate the downstream protein coding gene CACNA1C. In addition, miRNA-328 could partly reverse the effects of TCONS_00075467 on electrical remodeling. In summary, dysregulated lncRNAs may play important roles in modulating electrical remodeling during AF. Our study may facilitate the mechanism studies of lncRNAs in AF pathogenesis and provide potential therapeutic targets for AF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Probing and quantifying DNA-protein interactions with asymmetrical flow field-flow fractionation.

PubMed

Ashby, Jonathan; Schachermeyer, Samantha; Duan, Yaokai; Jimenez, Luis A; Zhong, Wenwan

2014-09-05

Tools capable of measuring binding affinities as well as amenable to downstream sequencing analysis are needed for study of DNA-protein interaction, particularly in discovery of new DNA sequences with affinity to diverse targets. Asymmetrical flow field-flow fractionation (AF4) is an open-channel separation technique that eliminates interference from column packing to the non-covalently bound complex and could potentially be applied for study of macromolecular interaction. The recovery and elution behaviors of the poly(dA)n strand and aptamers in AF4 were investigated. Good recovery of ssDNAs was achieved by judicious selection of the channel membrane with consideration of the membrane pore diameter and the radius of gyration (Rg) of the ssDNA, which was obtained with the aid of a Molecular Dynamics tool. The Rg values were also used to assess the folding situation of aptamers based on their migration times in AF4. The interactions between two ssDNA aptamers and their respective protein components were investigated. Using AF4, near-baseline resolution between the free and protein-bound aptamer fractions could be obtained. With this information, dissociation constants of ∼16nM and ∼57nM were obtained for an IgE aptamer and a streptavidin aptamer, respectively. In addition, free and protein-bound IgE aptamer was extracted from the AF4 eluate and amplified, illustrating the potential of AF4 in screening ssDNAs with high affinity to targets. Our results demonstrate that AF4 is an effective tool holding several advantages over the existing techniques and should be useful for study of diverse macromolecular interaction systems. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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

Intra-operative mapping of the atria: the first step towards individualization of atrial fibrillation therapy?

PubMed

Kik, Charles; Mouws, Elisabeth M J P; Bogers, Ad J J C; de Groot, Natasja M S

2017-07-01

Atrial fibrillation (AF), an age-related progressive disease, is becoming a worldwide epidemic with a prevalence rate of 33 million. Areas covered: In this expert review, an overview of important results obtained from previous intra-operative mapping studies is provided. In addition, our novel intra-operative high resolution mapping studies, its surgical considerations and data analyses are discussed. Furthermore, the importance of high resolution mapping studies of both sinus rhythm and AF for the development of future AF therapy is underlined by our most recent results. Expert commentary: Progression of AF is determined by the extensiveness of electropathology which is defined as conduction disorders caused by structural damage of atrial tissue. The severity of electropathology is a major determinant of therapy failure. At present, we do not have any diagnostic tool to determine the degree of electropathology in the individual patient and we can thus not select the most optimal treatment modality for the individual patient. An intra-operative, high resolution scale, epicardial mapping approach combined with quantification of electrical parameters may serve as a diagnostic tool to stage AF in the individual patient and to provide patient tailored therapy.

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 ...

Electrical treatment of atrial arrhythmias in heart failure patients implanted with a dual defibrillator CRT device. Results from the TRADE-HF study.

PubMed

Botto, Giovanni Luca; Padeletti, Luigi; Covino, Gregorio; Pieragnoli, Paolo; Liccardo, Mattia; Mariconti, Barbara; Favale, Stefano; Molon, Giulio; De Filippo, Paolo; Bolognese, Leonardo; Landolina, Maurizio; Raciti, Giovanni; Boriani, Giuseppe

2017-06-01

Ventricular and atrial arrhythmias commonly occur in heart failure patients and are a significant source of symptoms, morbidity and mortality. Some specific generators referred to as dual defibrillators, Dual CRT-Ds, have the ability to treat atrial and ventricular arrhythmias. TRADE-HF is a prospective two-arm randomized study aimed at assessing the benefits of complete automatic management of atrial arrhythmias in patients implanted with a dual CRT-D. Primary objective of the TRADE-HF study was to document reduction of unplanned hospital admission for cardiac reasons or death for cardiovascular causes or progression to permanent AF, by comparing fully-automatic device driven therapy for atrial tachycardia or fibrillation (AT/AF) to an in-hospital approach for treatment of symptomatic AT/AF. Randomized Patients were followed every 6months for 3years to assess the primary objective. Four-hundred-twenty patients have been enrolled in the study. At the end of the study 30 subjects died for cardiovascular causes, 60 had at least one hospitalization for cardiovascular causes and 14 developed permanent AF. Eighty-seven patients experienced a composite event. Hazard Ratio for device-managed automatic therapy arm compared to traditional was 0.987 (95% CI: 0.684-1.503; p=0.951). The primary endpoint analysis resulted in no difference between the device managed and in-hospital treatment arm. The TRADE-HF study failed to demonstrate a reduction in the composite of unplanned hospitalizations for cardiovascular causes or death for cardiovascular causes or progression to permanent AF using automatic atrial therapy compared to a traditional approach including hospitalization for symptomatic episodes and/or in-hospital treatment of AT/AF. Copyright © 2017 Elsevier B.V. All rights reserved.

Dronedarone: a promising alternative for the management of atrial fibrillation.

PubMed

Yalta, Kenan; Turgut, Okan Onur; Yilmaz, Mehmet Birhan; Yilmaz, Ahmet; Tandogan, Izzet

2009-10-01

Atrial fibrillation (AF) is the most frequently encountered chronic arrhythmia associated with significant morbidity. It is generally encountered in the elderly, and will presumably become more prevalent in the future due to the increasing proportion of the elderly in the population. Major studies on AF have demonstrated no significant difference between rhythm and rate control in terms of mortality. However, young population with new-onset or lone AF, or patients in whom the maintenance of sinus rhythm is a must (due to recurrent thromboembolic events etc.) still gives rise to significant concerns related to the obligatory long-term prophylaxis. The long-term administration of the currently available conventional agents (amiodarone, dofetilide, sotalol, propafenone,flecainide etc.) is considered as a 'double edged sword' due to the presence of life-threatening adverse effects including pro-arrhythmia and organ toxicity associated with these agents. Several molecules are being developed for the management of AF. However, only a few novel agents confer promising results with respect to safety and efficacy issues in the major studies. Dronedarone is an amiodarone analogue without iodine moiety in its structure, and is similar to amiodarone with regard to its structural and electrophysiological properties. Dronedarone is largely denuded of the potentially life-threatening adverse effects of anti-arrhythmics. Major clinical studies have demonstrated both rhythm and rate-controlling efficacy of dronedarone compared to placebo without any serious adverse effects in patients with AF. However, the ANDROMEDA trial, a large scale study including patients hospitalized for symptomatic congestive heart failure (with severely depressed left ventricular systolic functions) was prematurely terminated due to the increased mortality in the dronedarone arm compared to placebo indicating a lack of safety in this group of patients. Conversely, the recently published ATHENA study (including more than 4,600 high risk patients, but excluding those with severe heart failure) demonstrated a significant reduction in cardiovascular hospitalizations and cardiovascular mortality with dronedarone compared to placebo. In contrast, the DIONYSOS study, comparing dronedarone with amiodarone, demonstrated better safety, but lower efficacy of dronedarone for the maintenance of sinus rhythm in patients with AF. Further clinical trials (including head to head comparison with other conventional anti-arrhythmics) are still required to determine the place of dronedarone in the management of AF. The present review focuses on basic and clinical aspects of dronedarone, a novel agent for the management of 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

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

PubMed

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

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

Biomarkers of Inflammation, Thrombogenesis, and Collagen Turnover in Patients With Atrial Fibrillation.

PubMed

Jabati, Sallu; Fareed, Jawed; Liles, Jeffrey; Otto, Abigail; Hoppensteadt, Debra; Bontekoe, Jack; Phan, Trung; Walborn, Amanda; Syed, Mushabbar

2018-07-01

The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF. Baseline plasma was collected from patients with AF prior to ablation surgery at Loyola University Medical Center. Individuals with AF had statistically significantly increased levels of PAI-1, CD40-L, and nucleosomes, when compared to the normal population ( P < .0001). Additionally, there was a statistically significant increase in the CRP ( P = .01), PIIINP ( P = .04), and PIIICP ( P = .0008) when compared to normal individuals. From this study, it is concluded that the prothrombotic, inflammatory, and collagen turnover biomarkers PAI-1, CD40-L, nucleosomes, CRP, PIIICP, and PIIINP are elevated in AF.

Iron-based ferritin nanocore as a contrast agent.

PubMed

Sana, Barindra; Johnson, Eric; Sheah, Kenneth; Poh, Chueh Loo; Lim, Sierin

2010-09-01

Self-assembling protein cages have been exploited as templates for nanoparticle synthesis. The ferritin molecule, a protein cage present in most living systems, stores excess soluble ferrous iron in the form of an insoluble ferric complex within its cavity. Magnetic nanocores formed by loading excess iron within an engineered ferritin from Archaeoglobus fulgidus (AfFtn-AA) were studied as a potential magnetic resonance (MR) imaging contrast agent. The self-assembly characteristics of the AfFtn-AA were investigated using dynamic light scattering technique and size exclusion chromatography. Homogeneous size distribution of the assembled nanoparticles was observed using transmission electron microscopy. The magnetic properties of iron-loaded AfFtn-AA were studied using vibrating sample magnetometry. Images obtained from a 3.0 T whole-body MRI scanner showed significant brightening of T(1) images and signal loss of T(2) images with increased concentrations of iron-loaded AfFtn-AA. The analysis of the MR image intensities showed extremely high R(2) values (5300 mM(-1) s(-1)) for the iron-loaded AfFtn-AA confirming its potential as a T(2) contrast agent.

iPhone ECG screening by practice nurses and receptionists for atrial fibrillation in general practice: the GP-SEARCH qualitative pilot study.

PubMed

Orchard, Jessica; Freedman, Saul Benedict; Lowres, Nicole; Peiris, David; Neubeck, Lis

2014-05-01

Atrial fibrillation (AF) is often asymptomatic and substantially increases stroke risk. A single-lead iPhone electrocardiograph (iECG) with a validated AF algorithm could make systematic AF screening feasible in general practice. A qualitative screening pilot study was conducted in three practices. Receptionists and practice nurses screened patients aged ≥65 years using an iECG (transmitted to a secure website) and general practitioner (GP) review was then provided during the patient's consultation. Fourteen semi-structured interviews with GPs, nurses, receptionists and patients were audio-recorded, transcribed and analysed thematically. Eighty-eight patients (51% male; mean age 74.8 ± 8.8 years) were screened: 17 patients (19%) were in AF (all previously diagnosed). The iECG was well accepted by GPs, nurses and patients. Receptionists were reluctant, whereas nurses were confident in using the device, explaining and providing screening. AF screening in general practice is feasible. A promising model is likely to be one delivered by a practice nurse, but depends on relevant contextual factors for each practice.

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.

A novel method for determination of aflatoxin B1 mediated by FCLA + BSA

NASA Astrophysics Data System (ADS)

Chen, WenLi; Xing, Da

2005-02-01

As a chemiluminescence (CL) probe, 3,7-dihydro-6-{4-{2-(N"-(5-fluoresceinyl) thioureido)ethoxy}phenyl}-2-met -hylimi-dazo{1,2-a}pyrazin-3-one dosium salt (FCLA) can sensitively and specifically react with singlet oxygen (1O2 ) and superoxide(O2""). BSA (Bovine Serum Albumin) can enlarge the CL intensity of FCLA to 860%. This report presents a novel method for determination of Aflatoxin B1 (AfB1) mediated by FCLA+BSA. The concentration of AFB1 showed an obvious positive correlation with the CL intensity mediated by FCLA+BSA. This method could measure accurately ng/ml of AfB1 concentration. At the same time, the fluorescence spectrum of FCLA+BSA and FCLA+BSA+AfB1 were measured respectively, which showed that the fluorescence intensity of FCLA+BSA+AfB1 was higher than FCLA+BSA. Comparing the peak value of FCLA, FCLA+BSA and FCLA+BSA+AfB1 had a 6nm Einstein shift (red shift). The study suggested that CL method mediated by FCLA+BSA might be applicable to the determination of AfB1 concentration.

Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation

PubMed Central

Tsai, Chia-Ti; Hsieh, Chia-Shan; Chang, Sheng-Nan; Chuang, Eric Y.; Ueng, Kwo-Chang; Tsai, Chin-Feng; Lin, Tsung-Hsien; Wu, Cho-Kai; Lee, Jen-Kuang; Lin, Lian-Yu; Wang, Yi-Chih; Yu, Chih-Chieh; Lai, Ling-Ping; Tseng, Chuen-Den; Hwang, Juey-Jen; Chiang, Fu-Tien; Lin, Jiunn-Lee

2016-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10−24). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway. PMID:26831368

How to Make Feedback More Effective? Qualitative Findings from Pilot Testing of an Audit and Feedback Report for Endoscopists

PubMed Central

Webster, Fiona; Patel, Jigisha; Rice, Kathleen; Baxter, Nancy; Paszat, Lawrence; Rabeneck, Linda

2016-01-01

Background. Audit and feedback (A/F) reports are one of the few knowledge translation activities that can effect change in physician behavior. In this study, we pilot-tested an endoscopist A/F report to elicit opinions about the proposed report's usability, acceptability and usefulness, and implications for knowledge translation. Methods. Semi-structured qualitative interviews were conducted with eleven endoscopists in Ontario, Canada. We tested an A/F report template comprising 9 validated, accepted colonoscopy quality indicators populated with simulated data. Interview transcripts were coded using techniques such as constant comparison and themes were identified inductively over several team meetings. Results. Four interrelated themes were identified: (1) overall perceptions of the A/F report; (2) accountability and consequences for poor performance; (3) motivation to change/improve skills; and (4) training for performance enhancement and available resources. The A/F report was well received; however, participants cited some possible threats to the report's effectiveness including the perceived threat of loss of privileges or licensing and the potential for the data to be dismissed. Conclusions. Participants agreed that A/F has the potential to improve colonoscopy performance. However, in order to be effective in changing physician behavior, A/F must be thoughtfully implemented with attention to the potential concerns of its recipients. PMID:27722149

Preoperative atrial fibrillation and long-term survival after open heart surgery in a rural tertiary heart institute.

PubMed

O'Neal, Wesley T; Efird, Jimmy T; Davies, Stephen W; Choi, Yuk Ming; Anderson, Curtis A; Kindell, Linda C; O'Neal, Jason B; Ferguson, T Bruce; Chitwood, W Randolph; Kypson, Alan P

2013-01-01

Preoperative atrial fibrillation (AF) is associated with increased morbidity and mortality after open heart surgery. However, the impact of preoperative AF on long-term survival after open heart surgery has not been widely examined in rural populations. Patients from rural regions are less likely to receive treatment for cardiac conditions and to have adequate medical insurance coverage. To examine the influence of preoperative AF on long-term survival following open heart surgery in rural eastern North Carolina. Long-term survival was compared in patients with and without preoperative AF after coronary artery bypass grafting (CABG) and CABG plus valve (CABG + V) surgery between 2002 and 2011. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. The study population consisted of 5438 patients. A total of 263 (5%) patients had preoperative AF. Preoperative AF was an independent predictor of long-term survival (open heart surgery: adjusted HR = 1.6, 95% CI = 1.3-2.0; CABG: adjusted HR = 1.6, 95% CI = 1.3-2.1; CABG + V: adjusted HR = 1.6, 95% CI = 1.1-2.3). Preoperative AF is an important predictor of long-term survival after open heart surgery in this rural population. Copyright © 2013 Elsevier Inc. All rights reserved.

Halophilic viruses with varying biochemical and biophysical properties are amenable to purification with asymmetrical flow field-flow fractionation.

PubMed

Eskelin, Katri; Lampi, Mirka; Meier, Florian; Moldenhauer, Evelin; Bamford, Dennis H; Oksanen, Hanna M

2017-11-01

Viruses come in various shapes and sizes, and a number of viruses originate from extremities, e.g. high salinity or elevated temperature. One challenge for studying extreme viruses is to find efficient purification conditions where viruses maintain their infectivity. Asymmetrical flow field-flow fractionation (AF4) is a gentle native chromatography-like technique for size-based separation. It does not have solid stationary phase and the mobile phase composition is readily adjustable according to the sample needs. Due to the high separation power of specimens up to 50 µm, AF4 is suitable for virus purification. Here, we applied AF4 for extremophilic viruses representing four morphotypes: lemon-shaped, tailed and tailless icosahedral, as well as pleomorphic enveloped. AF4 was applied to input samples of different purity: crude supernatants of infected cultures, polyethylene glycol-precipitated viruses and viruses purified by ultracentrifugation. All four virus morphotypes were successfully purified by AF4. AF4 purification of culture supernatants or polyethylene glycol-precipitated viruses yielded high recoveries, and the purities were comparable to those obtained by the multistep ultracentrifugation purification methods. In addition, we also demonstrate that AF4 is a rapid monitoring tool for virus production in slowly growing host cells living in extreme conditions.

Vitamin D and new-onset atrial fibrillation: A meta-analysis of randomized controlled trials.

PubMed

Huang, Wei-Ling; Yang, Jun; Yang, Jian; Wang, Hui-Bo; Yang, Chao-Jun; Yang, Ying

2017-11-14

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which affects 1.5% to 2% of the general population. More than six million Europeans suffer from AF. To research vitamin D levels in the prevention of new-onset atrial fibrillation (AF), we conducted a systematic review of randomized controlled trials (RCTs). We focused on the vitamin D levels in the prevention of new-onset AF. The outcomes assessed were vitamin D levels, left ventricular ejection fraction (LVEF), and left atrium diameter. Six RCTs ultimately met the inclusion criteria in the meta-analysis. The outcomes of Vitamin D levels (MD = -4.27, 95% CI = -5.20 to-3.34, P = 0.30) in the new-onset AF showed no significant difference. The left atrium diameter (MD = 1.96, 95% CI = 1.48 to 2.60, P < 0.01) between new-onset AF and LVEF (MD = -0.92, 95% CI = -1.59 to -0.26, P < 0.01) showed significant difference. Our study shows that circulating vitamin D levels may not play a major role in the development of new-onset AF. Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.