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      Features of atrial fibrillation in wild‐type transthyretin cardiac amyloidosis: a systematic review and clinical experience

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          Abstract

          Aims

          Wild‐type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) commonly affects older adults with heart failure and is associated with reduced survival, but its role in ATTRwt is unclear. We sought to explore the clinical impact of AF in ATTRwt.

          Methods and results

          Patients with biopsy‐proven ATTRwt cardiac amyloidosis ( n = 146) were retrospectively identified, and clinical, echocardiographic, and biochemical data were collected. Patients were classified as AF or non‐AF and followed for survival for a median of 41.4 ± 27.1 months. Means testing, univariable, and multivariable regression models were employed. A systematic review was performed. AF was observed in 70% ( n = 102). Mean age was similar (AF, 75 ± 6 vs. non‐AF, 74 ± 5 years, P = 0.22). Anticoagulant treatment of patients with AF was as follows: 78% warfarin, 17% novel anticoagulant, and 6% no anticoagulation. Amiodarone was prescribed to 24%. There were no differences in left ventricular ejection fraction ( P = 0.09) or left atrial volume ( P = 0.87); however, mean diastolic dysfunction grade was higher in AF (mean 2.7 ± 0.5 vs. 2.4 ± 0.5, P = 0.01). While creatinine ( P = 0.52) and B‐type natriuretic peptide ( P = 0.48) were similar, patients with AF had lower serum transthyretin concentrations (221 ± 51 vs. 250 ± 52 μg/mL, P < 0.01). Survival between groups was similar ( P = 0.46).

          Conclusions

          These data provide an evidence basis for clinical management and demonstrate that AF in ATTRwt does not negatively impact survival. Further analysis of the relationship between transthyretin concentration and AF development is warranted.

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          Most cited references12

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          Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study.

          To determine the independent risk factors for atrial fibrillation. Cohort study. The Framingham Heart Study. A total of 2090 men and 2641 women members of the original cohort, free of a history of atrial fibrillation, between the ages of 55 and 94 years. Sex-specific multiple logistic regression models to identify independent risk factors for atrial fibrillation, including age, smoking, diabetes, electrocardiographic left ventricular hypertrophy, hypertension, myocardial infarction, congestive heart failure, and valve disease. During up to 38 years of follow-up, 264 men and 298 women developed atrial fibrillation. After adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times greater risk of developing atrial fibrillation than women. In the full multivariable model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age was 2.1 for men and 2.2 for women (P < .0001). In addition, after multivariable adjustment, diabetes (OR, 1.4 for men and 1.6 for women), hypertension (OR, 1.5 for men and 1.4 for women), congestive heart failure (OR, 4.5 for men and 5.9 for women), and valve disease (OR, 1.8 for men and 3.4 for women) were significantly associated with risk for atrial fibrillation in both sexes. Myocardial infarction (OR, 1.4) was significantly associated with the development of atrial fibrillation in men. Women were significantly more likely than men to have valvular heart disease as a risk factor for atrial fibrillation. The multivariable models were largely unchanged after eliminating subjects with valvular heart disease. In addition to intrinsic cardiac causes such as valve disease and congestive heart failure, risk factors for cardiovascular disease also predispose to atrial fibrillation. Modification of risk factors for cardiovascular disease may have the added benefit of diminishing the incidence of atrial fibrillation.
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            Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes.

            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.
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              Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk factors and prognostic role.

              Although atrial fibrillation (AF) is a known complication of amyloidotic cardiomyopathy (AC), a precise pathophysiological and prognostic characterization is not available. We therefore aimed to assess prevalence, incidence, risk factors and prognostic significance of AF in light-chain (AL), hereditary transthyretin-related (m-ATTR) and non-mutant transthyretin-related (wt-ATTR) AC.
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                Author and article information

                Contributors
                frruberg@bu.edu
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                19 June 2018
                October 2018
                : 5
                : 5 ( doiID: 10.1002/ehf2.v5.5 )
                : 772-779
                Affiliations
                [ 1 ] Department of Medicine Boston Medical Center Boston MA USA
                [ 2 ] Department of Biostatistics Boston University School of Public Health Boston MA USA
                [ 3 ] Amyloidosis Center Boston University School of Medicine, Boston Medical Center Boston MA USA
                [ 4 ] Department of Pathology and Laboratory Medicine Boston University School of Medicine, Boston Medical Center Boston MA USA
                [ 5 ] Section of Cardiovascular Medicine, Department of Medicine Boston University School of Medicine, Boston Medical Center Boston MA USA
                Author notes
                [*] [* ] Correspondence to: Frederick L. Ruberg, Section of Cardiovascular Medicine, Boston Medical Center, 88 E. Newton Street, Boston, MA 02118, USA. Tel: 617 638 8968; Fax: 617 638 8969.

                Email: frruberg@ 123456bu.edu

                Article
                EHF212308 ESCHF-18-00032
                10.1002/ehf2.12308
                6165925
                29916559
                0ebb39d3-89ed-43e2-93a0-4108a98d6338
                © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 01 February 2018
                : 06 April 2018
                : 30 April 2018
                Page count
                Figures: 3, Tables: 3, Pages: 8, Words: 3282
                Funding
                Funded by: NIH
                Award ID: R21 AG R21AG050206
                Award ID: R01 AG031804
                Funded by: Young Family Amyloid Research Fund
                Categories
                Original Research Article
                Original Research Articles
                Custom metadata
                2.0
                ehf212308
                October 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0 mode:remove_FC converted:01.10.2018

                cardiac amyloidosis,transthyretin,atrial fibrillation

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