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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

Pitx2c and Nkx2-5 Are Required for the Formation and Identity of the Pulmonary Myocardium

TL;DR: A cellular mechanism for pulmonary myocardium formation is suggested and the key roles played by Pitx2c and Nkx2-5 in its formation and identity are highlighted.
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Molecular Pathway for the Localized Formation of the Sinoatrial Node

TL;DR: The molecular pathway provides a mechanism for how pacemaker activity becomes progressively relegated to the most recently added components of the venous pole of the heart and, ultimately, to the junction of the right atrium and superior caval vein.
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CaMKII-Dependent Diastolic SR Ca2+ Leak and Elevated Diastolic Ca2+ Levels in Right Atrial Myocardium of Patients With Atrial Fibrillation

TL;DR: In this article, the authors tested the hypothesis that CaMKII-dependent diastolic sarcoplasmic reticulum (SR) Ca2+ leak and elevated dastolic ca2+ levels occurs in atrial myocardium of patients with AF.
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Defective Cardiac Ryanodine Receptor Regulation During Atrial Fibrillation

TL;DR: Atrial tissue from both the AF dogs and humans with chronic AF showed a significant increase in PKA phosphorylation of RyR2, with a corresponding decrease in calstabin2 binding to the channel.
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Molecular Basis of Downregulation of G-Protein–Coupled Inward Rectifying K+ Current (IK,ACh) in Chronic Human Atrial Fibrillation Decrease in GIRK4 mRNA Correlates With Reduced IK,ACh and Muscarinic Receptor–Mediated Shortening of Action Potentials

TL;DR: It is suggested that atrial myocytes adapt to a chronically high rate by downregulating IK,ACh to counteract the shortening of the atrial effective refractory period due to electrical remodeling.
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