Project description:BackgroundLittle is known about the relationship between coagulation biomarkers and clinical outcomes in patients with atrial fibrillation (AF) treated with anticoagulants, especially direct oral anticoagulants (DOACs) and warfarin.ObjectivesThis subcohort study evaluated the association between coagulation biomarkers and clinical outcomes in elderly Japanese patients with nonvalvular AF using the ANAFIE (All Nippon AF In the Elderly) Registry.MethodsPatients with a definitive diagnosis of nonvalvular AF and aged ≥75 years at enrollment were included. At enrollment, biomarker levels for D-dimer, thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), and soluble fibrin monomer complex (SFMC), along with data on anticoagulant use, were recorded.ResultsOf the 3,194 patients, 95.1% were using oral anticoagulants (OACs) (71.7% DOACs, 23.4% warfarin). D-dimer, TAT, and F1+2 levels, as well as the proportion of patients with a positive SFMC, were lower among those receiving OACs compared with those not receiving OACs. In the DOAC group, higher levels of D-dimer (≥1.0 μg/mL) and TAT (>3 ng/mL) were significantly associated with increased incidences of cardiovascular (CV) events (stroke, myocardial infarction, cardiac intervention, heart failure, and CV death), all-cause death, and CV death. In the warfarin group, higher levels of D-dimer were significantly associated with increased rates of all-cause death, higher levels of TAT with increased major bleeding, and positive SFMC with increased major bleeding and CV events.ConclusionsHigher levels of coagulation biomarkers were associated with a higher risk of worse clinical outcomes, and the relationships between the coagulation biomarkers and outcomes differed between the DOAC and warfarin groups. (Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation All Nippon AF In Elderly Registry-ANAFIE Registry; UMIN000024006).
Project description:Atrial fibrillation (AF), the most common clinically relevant arrhythmia, affects 2.2 million individuals in the USA and 4.5 million in Europe, resulting in significant morbidity and mortality. Pharmacotherapy aimed at controlling both heart rate and rhythm is employed to relieve AF symptoms, though debate continues about which approach is preferable. AF prevalence rises with age from 0.4% to 1% in the general population to 11% in those aged >70 years. AF is associated with a pro-thrombotic state and other comorbidities; age, hypertension, heart failure and diabetes mellitus all play a key role in AF pathogenesis. Anti-coagulation is essential for stroke prevention in patients with AF and is recommended for patients with one or more risk factors for stroke. Used within the recommended therapeutic range, warfarin and other vitamin K antagonists decrease the incidence of stroke and mortality in AF patients. Warfarin remains under-used, however, because of the perceived high risk of haemorrhage, narrow therapeutic window and need for regular monitoring. Several novel anti-coagulants show promise in AF-related stroke prevention. In particular, the novel, oral, direct thrombin inhibitor, dabigatran etexilate, recently licensed by the US Food and Drug Administration (FDA) and Health Canada has shown improved efficacy and safety compared with warfarin for stroke prevention in AF, and has the potential to replace warfarin in this indication. The increasing number of new therapeutic options, including improved anti-arrhythmic agents, novel anti-coagulants and more accessible ablation techniques, are likely to deliver better care for AF patients in the near future.
Project description:Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in preventing protein aggregation upon exposure to high levels of oxidants (molecular chaperone activity), and the transduction of redox signals to downstream proteins (redox switch activity). Mice lacking the peroxiredoxin Prdx1 exhibit an increased incidence of tumor formation, whereas baker's yeast (Saccharomyces cerevisiae) lacking the orthologous peroxiredoxin Tsa1 exhibit a mutator phenotype. Collectively, these findings suggest a potential link between peroxiredoxins, control of genomic stability, and cancer etiology. Here, we examine the potential mechanisms through which Tsa1 lowers mutation rates, taking into account its diverse biochemical roles in oxidant defense, protein homeostasis, and redox signaling as well as its interplay with thioredoxin and thioredoxin substrates, including ribonucleotide reductase. More work is needed to clarify the nuanced mechanism(s) through which this highly conserved peroxidase influences genome stability, and to determine if this mechanism is similar across a range of species.
Project description:The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established that advanced age, male sex, and European ancestry are prominent AF risk factors. Other modifiable risk factors include sedentary lifestyle, smoking, obesity, diabetes mellitus, obstructive sleep apnea, and elevated blood pressure predispose to AF, and each factor has been shown to induce structural and electric remodeling of the atria. Both heart failure and myocardial infarction increase risk of AF and vice versa creating a feed-forward loop that increases mortality. Other cardiovascular outcomes attributed to AF, including stroke and thromboembolism, are well established, and epidemiology studies have championed therapeutics that mitigate these adverse outcomes. However, the role of anticoagulation for preventing dementia attributed to AF is less established. Our review is a comprehensive examination of the epidemiological data associating unmodifiable and modifiable risk factors for AF and of the pathophysiological evidence supporting the mechanistic link between each risk factor and AF genesis. Our review also critically examines the epidemiological data on clinical outcomes attributed to AF and summarizes current evidence linking each outcome with AF.
Project description:Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation (AF).We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation (OAC; warfarin or novel oral anticoagulants [NOAC]). Secondary outcomes of interest included the proportion of patients prescribed NOACs (dabigatran or rivaroxaban); time in therapeutic range (TTR) for warfarin users, all-cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P=0.079), but less likely to receive NOAC at baseline or follow-up (12.1% vs 16.3%; unadjusted P=0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [OR]=0.68; 95% CI=0.49, 0.94), but was not associated with OAC use overall (OR=0.82; 95% CI=0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P<0.0001; adjusted TTR difference, -2.9; 95% CI=-5.7, -0.2; P=0.04). Use of an NOAC over 2 years of follow-up was not statistically different by insurance. Compared with non-Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics.In a contemporary AF cohort, use of OAC overall and use of NOACs were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.
Project description:BackgroundPrior studies have suggested that patients with atrial fibrillation (AF) referred for left atrial appendage occlusion (LAAO) are confronted with considerable risk of periprocedural thromboembolism and hemmorhagic events. The purpose of this study was to evaluate the safety and feasibility of bivalirudin during LAAO.MethodsThis retrospective, observational study included 420 AF patients who were evaluated as being at high risk of stroke or bleeding and indicated for LAAO at our center between June 2018 and June 2019 (158 with bivalirudin and 262 with heparin). The primary outcome was the incidence of any bleeding within 48 hours of LAAO. Secondary outcomes were major adverse cardiac events (MACE) between 48 hours and 60 days post-procedure and overall bleeding events during follow up.ResultsNo significant difference was observed between bivalirudin and heparin for major periprocedural bleeding (1.27% for bivalirudin vs. 2.29% for heparin, P=0.716) or minor bleeding (1.27% vs. 1.15%, P>0.9). At 48 hours post-procedure, strokes occurred at a rate of 0.63% in the bivalirudin group and 1.15% in the heparin group (P>0.9), and one case treated with bivalirudin developed systemic embolization. At 60 days, the rates of MACE (1.90% vs. 2.29%, P>0.9), a device-related thrombus (DRT) (1.27% vs. 1.52%, P>0.9), and overall bleeding events (5.06% vs. 4.96%, P=0.963) were comparable between the 2 cohorts. Upon Kaplan-Meier survival analysis, early safety during the 60-day follow-up was 93.67% in the bivalirudin group and 91.60% in the heparin group (P=0.570).ConclusionsBivalirudin has a comparable safety and efficacy profile to heparin as an intraprocedural anticoagulant, but currently, it should still be reserved for patients in which heparin is contraindicated.
Project description:Electrical and structural remodeling processes are contributors to the self-perpetuating nature of atrial fibrillation (AF). However, their correlation has not been clarified. In this study, human atrial tissues from the patients with rheumatic mitral valve disease in either sinus rhythm or persistent AF were analyzed using a combined transcriptomic and proteomic approach. An up-regulation in chloride intracellular channel (CLIC) 1, 4, 5 and a rise in type IV collagen were revealed. Combined with the results from immunohistochemistry and electron microscope analysis, the distribution of type IV collagen and effects of fibrosis on myocyte membrane indicated the possible interaction between CLIC and type IV collagen, confirmed by protein structure prediction and co-immunoprecipitation. These results indicate that CLICs play an important role in the development of atrial fibrillation and that CLICs and structural type IV collagen may interact on each other to promote the development of AF in rheumatic mitral valve disease.
Project description:BackgroundThere is limited information on the prognostic impact of new onset versus preexistent atrial fibrillation (AF) in hospitalized patients with cancer.ObjectivesWe sought to determine the clinical impact of new onset AF (NOAF) compared with preexistent AF in hospitalized patients with cancer.MethodsAll patients with cancer hospitalized over the course of 1 year with clinically manifest new or preexistent AF were enrolled in the Memorial Sloan Kettering Cancer Center AF registry. The relationship of NOAF to the primary composite outcome of all cause death, cardiovascular (CV) rehospitalization, or cerebrovascular event (CVE), as well as secondary CV endpoints, were analysed using proportional hazards regression. Where applicable, the competing risk of death was accounted for using methodology described by Fine and Gray.ResultsAmong 606 patients included in the analysis, 313 (51.7%) had NOAF and 293 (48.3%) had preexistent AF. Patients with NOAF were younger and had less frequent prior history of CV disease compared with patients with preexistent AF. At follow-up, patients with NOAF had a higher adjusted hazard for the primary composite outcome versus patients with prior AF (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.27, 2.13, P = 0.002), as well as the secondary CV composite outcome of clinical AF recurrence, CV death, CV rehospitalization, or CVE (HR 2.17, 95% CI 1.57, 2.99, P < 0.0001).ConclusionsIn hospitalized patients with cancer and electrocardiographically manifest new versus preexistent AF, NOAF was associated with a higher risk for the primary composite outcome of all-cause death, CV rehospitalization, or CVE.