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Concept: Atrial fibrillation

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Background In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed. Methods We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months. Results A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate. Conclusions The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367 .).

Concepts: Clinical trial, Myocardial infarction, Stroke, Atrial fibrillation, Pulmonary embolism, Tissue plasminogen activator, Thrombolysis, Plasmin

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 To determine whether atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men.

Concepts: Medicine, Epidemiology, Disease, Heart, Atrial fibrillation, Actuarial science

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Background It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. Methods We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. Results In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). Conclusions In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474 .).

Concepts: Blood, Stroke, Atrial fibrillation, Thrombosis, Pulmonary embolism, Warfarin, Anticoagulant, Heparin

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Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Phase III trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin excluded patients with moderate/severe mitral stenosis or mechanical heart valves, but variably included patients with other VHD and valve surgeries.

Concepts: Atrial fibrillation

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Atrial fibrillation is a common arrhythmia in heart failure and a risk factor for stroke. Risk assessment tools can assist clinicians with decision making in the allocation of thromboprophylaxis. This review provides an overview of current validated risk assessment tools for atrial fibrillation and emphasizes the importance of tailoring individual risk and the importance of weighing the benefits of treatment. Further, this review provides details of innovative and patient-centered methods for ensuring optimal adherence to prescribed therapy. Prior to initiating oral anticoagulant therapy, a comprehensive risk assessment should include evaluation of associated cardiogeriatric conditions, potential for adherence to prescribed therapy, frailty, and functional and cognitive ability.

Concepts: Decision making, Evaluation, Heart, Risk, Atrial fibrillation, Cognition, Decision theory, Anticoagulant

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Atrial fibrillation (AF) is a common arrhythmia of substantial public health importance. Recent evidence demonstrates a heritable component underlying AF, and genetic discoveries have identified common variants associated with the arrhythmia. Ultimately one hopes that the consideration of genetic variation in clinical practice may enhance care and improve health outcomes. In this review we explore areas of potential clinical utility in AF management including those relating to pharmacogenetics and risk prediction.

Concepts: Health care, Pharmacology, Medicine, Public health, Genetics, Health, Clinical trial, Atrial fibrillation

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Oral anticoagulant therapy is used to prevent thrombosis in patients with atrial fibrillation (AF), venous thrombosis and prosthetic heart valves. The introduction of new therapies emphasizes the need to discern the best practice for the patients remaining on warfarin treatment. This study compares patient characteristics and therapeutic control in two settings managing warfarin treatment: Swedish primary health care centers (PHCC) and specialized anticoagulation clinics (ACC).

Concepts: Medicine, Stroke, Atrial fibrillation, Thrombosis, Warfarin, Anticoagulant, Heparin, Prothrombin time

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INTRODUCTION AND OBJECTIVES: Left atrial appendage closure can be an attractive option for patients with nonvalvular atrial fibrillation and a contraindication to oral anticoagulants, provided that satisfactory results can be achieved during implantation and follow-up. METHODS: Thirty-five consecutive patients, not eligible for randomized trials with oral anticoagulants, had an Amplatzer occlusion device implanted under general anesthesia. After the first 5 patients, 3-dimensional imaging was incorporated. The results of the implantation and the follow-up were analyzed over a 1-year period. RESULTS: The mean age was 74.65 (7.61) years, with a CHADS(2) score of 2.41 (1.53) and a CHA(2)DS(2)-VASc score of 3.17 (1.60). Implantation failed in 1 patient and 5 needed a change in the selected plug size. There were no cardiac complications during the implantation or hospital stay. There was 1 vascular complication (arteriovenous fistula). Transesophageal echocardiography monitoring was performed at 24h, 1, 3, 6 and 12 months and we found 5 thrombi which were resolved with heparin. In the follow-up period of 21.14 (10.09) months, 3 patients aged>80 years died, none of them due to heart problems, and one transient ischemic stroke without further consequences. CONCLUSIONS: Left atrial appendage closure by an experienced operator can be a treatment option with few complications and with efficient results at>1 year in reducing thromboembolic and hemorrhagic complications, even in very high-risk groups. Full English text available from:www.revespcardiol.org/en.

Concepts: Cardiology, Heart, Stroke, Atrial fibrillation, Warfarin, Anticoagulant, Heparin, Left atrial appendage

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Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

Concepts: Genetics, Atrial fibrillation, Hypothyroidism, Hyperthyroidism, Thyroid, Thyroid hormone, Endocrine system, Triiodothyronine

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Atrial fibrillation, the commonest cardiac arrhythmia, predisposes to thrombus formation and consequently increases risk of ischaemic stroke. Recent years have seen approval of a number of novel oral anticoagulants. Nevertheless, warfarin and aspirin remain the mainstays of therapy. It is widely appreciated that both these agents increase the likelihood of bleeding: there is a popular conception that this risk is greater with warfarin. In fact, well-managed warfarin therapy (INR 2-3) has little effect on bleeding risk and is twice as effective as aspirin at preventing stroke. Patients with atrial fibrillation and a further risk factor for stroke (CHA2DS2-VASc >0) should therefore either receive warfarin or a novel oral agent. The remainder who are at the very lowest risk of stroke are better not prescribed antithrombotic therapy. For stroke prevention in atrial fibrillation; aspirin is rarely the right choice.

Concepts: Myocardial infarction, Stroke, Atrial fibrillation, Thrombosis, Warfarin, Thrombus, Anticoagulant, Heparin