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Recent advances in the molecular pathophysiology of atrial fibrillation

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TLDR
The ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia are discussed, including the potential therapeutic implications that might arise from an improved mechanistic understanding.
Abstract
Atrial fibrillation (AF) is an extremely common cardiac rhythm disorder that causes substantial morbidity and contributes to mortality. The mechanisms underlying AF are complex, involving both increased spontaneous ectopic firing of atrial cells and impulse reentry through atrial tissue. Over the past ten years, there has been enormous progress in understanding the underlying molecular pathobiology. This article reviews the basic mechanisms and molecular processes causing AF. We discuss the ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia. We conclude with a discussion of the potential therapeutic implications that might arise from an improved mechanistic understanding.

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Citations
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Journal ArticleDOI

2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design

Hugh Calkins, +60 more
- 01 Apr 2012 - 
TL;DR: This 2012 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a Task Force, convened by the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society and charged with defining the indications, techniques, and outcomes of this procedure.
Journal ArticleDOI

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary

TL;DR: The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease.
Journal ArticleDOI

2017 HRS / EHRA / ECAS / APHRS / SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

Hugh Calkins, +60 more
- 01 Oct 2017 - 
TL;DR: This 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group, convened by these five international societies.
Journal ArticleDOI

2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design

Hugh Calkins, +48 more
- 01 Jan 2012 - 
TL;DR: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation, developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology and the European Cardiac Arrhythmia Society (ECAS), was published in this paper.
References
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Journal ArticleDOI

Mutations in sodium channel β-subunit SCN3B are associated with early-onset lone atrial fibrillation

TL;DR: In 192 young lone AF patients, three patients are found with suspected disease-causing non-synonymous mutations in SCN3B, indicating that mutations in this gene contribute to the mechanism of lone AF, supporting the hypothesis that decreased sodium current enhances AF susceptibility.
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Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces ICa,Land Itoin rapid atrial pacing in rabbits

TL;DR: L-type calcium current and I(to) are reduced in early phases of electrical remodeling, a major mechanism appears to be transcriptional downregulation of underlying ion channels, which partially preceded ion current changes.
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Intracellular calcium leak due to FKBP12.6 deficiency in mice facilitates the inducibility of atrial fibrillation

TL;DR: The increased vulnerability to AF in FKBP 12.6-/- mice substantiates the notion that defective SR Ca(2+) release caused by abnormal RyR2 and FK BP12.6 interactions may contribute to the initiation or maintenance of atrial fibrillation.
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Differential phosphorylation-dependent regulation of constitutively active and muscarinic receptor-activated IK,ACh channels in patients with chronic atrial fibrillation.

TL;DR: In cAF, the higher protein level of PKCepsilon but not PKCalpha, PKCbeta1 or PKCdelta is likely to contribute to the constitutive IK,ACh activity, while selective drug targeting of constitutively active IK-ACh channels may be suitable to reduce the ability of AF to become sustained.
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Characterization of sustained atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure.

TL;DR: Inducible atrial tachyarrhythmias and electrophysiologic alterations in dogs with CHF and atrial enlargement produced by rapid ventricular pacing are characterized.
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