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.read more
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Journal ArticleDOI
Atrial Fibrillation Mechanisms and Implications for Catheter Ablation
Ghassen Cheniti,Konstantinos Vlachos,Thomas Pambrun,Darren A. Hooks,Antonio Frontera,Masateru Takigawa,Felix Bourier,Takeshi Kitamura,Anna Lam,Claire A. Martin,Carole Dumas-Pommier,Stéphane Puyo,Xavier Pillois,Josselin Duchateau,Nicolas Klotz,Arnaud Denis,Nicolas Derval,Pierre Jaïs,Hubert Cochet,Mélèze Hocini,Michel Haïssaguerre,Frederic Sacher +21 more
TL;DR: Evidence for structural remodeling, mainly represented by atrial fibrosis, suggests that reentrant activities using anatomical substrate are the key mechanism sustaining AF.
Journal ArticleDOI
Atrial arrhythmia, triggering events and conduction abnormalities in isolated murine RyR2-P2328S hearts.
TL;DR: The present experiments investigate the atrial electrophysiology of homozygotic murine RyR2‐P2328S (RyR2S/S) hearts for ectopic triggering events and for conduction abnormalities that might provide a re‐entrant substrate.
Journal ArticleDOI
Antihyperglycemic drugs use and new-onset atrial fibrillation: A population-based nested case control study.
TL;DR: The use of biguanides or thiazolidinediones may be associated with a low risk of developing NAF, whereas insulin may beassociated with a significant increase in the risk of NAF in patients with type 2 diabetes mellitus during long-term follow-up.
Journal ArticleDOI
The role of Epac in the heart
Takayuki Fujita,Masanari Umemura,Utako Yokoyama,Satoshi Okumura,Satoshi Okumura,Yoshihiro Ishikawa +5 more
TL;DR: It is shown that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions, and developing the ability to regulate cAMP-mediated signaling through Epac may lead to remarkable new therapies for the treatment of cardiac diseases.
Journal ArticleDOI
Further insights into the underlying electrophysiological mechanisms for reduction of atrial fibrillation by ranolazine in an experimental model of chronic heart failure
Gerrit Frommeyer,Marco Schmidt,Catharina Clauß,Sven Kaese,Jörg Stypmann,Christian Pott,Lars Eckardt,Peter Milberg +7 more
TL;DR: The underlying mechanisms for the antiarrhythmic benefit of RAN application in chronic heart failure (CHF) are examined.
References
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Journal ArticleDOI
Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins
Michel Haïssaguerre,Pierre Jaïs,D. C. Shah,Atsushi Takahashi,Mélèze Hocini,G Quiniou,S. Garrigue,A Le Mouroux,P Le Métayer,Jacques Clementy +9 more
TL;DR: The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation and these foci respond to treatment with radio-frequency ablation.
Journal ArticleDOI
Atrial Fibrillation Begets Atrial Fibrillation A Study in Awake Chronically Instrumented Goats
TL;DR: Artificial maintenance of AF leads to a marked shortening of AERP, a reversion of its physiological rate adaptation, and an increase in rate, inducibility and stability of AF.
Journal ArticleDOI
Secular Trends in Incidence of Atrial Fibrillation in Olmsted County, Minnesota, 1980 to 2000, and Implications on the Projections for Future Prevalence
Yoko Miyasaka,Marion E. Barnes,Bernard J. Gersh,Stephen S. Cha,Kent R. Bailey,Walter P. Abhayaratna,James B. Seward,Teresa S.M. Tsang +7 more
TL;DR: The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000 and the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.
Journal ArticleDOI
MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thomas Thum,Carina Gross,Jan Fiedler,Thomas Fischer,Stephan Kissler,Markus Bussen,Paolo Galuppo,Steffen Just,Wolfgang Rottbauer,Stefan Frantz,Mirco Castoldi,Jürgen Soutschek,Victor Koteliansky,Andreas Rosenwald,M. Albert Basson,Jonathan D. Licht,John T. R. Pena,Sara H. Rouhanifard,Martina U. Muckenthaler,Thomas Tuschl,Gail R. Martin,Johann Bauersachs,Stefan Engelhardt,Stefan Engelhardt +23 more
TL;DR: It is shown that microRNA-21 regulates the ERK–MAP kinase signalling pathway in cardiac fibroblasts, which has impacts on global cardiac structure and function and confirms miR-21 as a disease target in heart failure and establishes the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.
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Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis
Eva van Rooij,Lillian B. Sutherland,Jeffrey E. Thatcher,J. Michael DiMaio,R. Haris Naseem,William S. Marshall,Joseph A. Hill,Eric N. Olson +7 more
TL;DR: It is concluded that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.